Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression
Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similari...
Ausführliche Beschreibung
Autor*in: |
Carvalho, Brener C. [verfasserIn] Oliveira, Leonardo C. [verfasserIn] Rocha, Carolina D. [verfasserIn] Fernandes, Heliana B. [verfasserIn] Oliveira, Isadora M. [verfasserIn] Leão, Felipe B. [verfasserIn] Valverde, Thalita M. [verfasserIn] Rego, Igor M.G. [verfasserIn] Ghosh, Sankar [verfasserIn] Silva, Aristóbolo M. [verfasserIn] |
---|
Format: |
E-Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2019 |
---|
Schlagwörter: |
---|
Übergeordnetes Werk: |
Enthalten in: Molecular immunology - Amsterdam [u.a.] : Elsevier, 1979, 109, Seite 27-37 |
---|---|
Übergeordnetes Werk: |
volume:109 ; pages:27-37 |
DOI / URN: |
10.1016/j.molimm.2019.02.015 |
---|
Katalog-ID: |
ELV002032236 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | ELV002032236 | ||
003 | DE-627 | ||
005 | 20230524165102.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230429s2019 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.molimm.2019.02.015 |2 doi | |
035 | |a (DE-627)ELV002032236 | ||
035 | |a (ELSEVIER)S0161-5890(18)30761-2 | ||
040 | |a DE-627 |b ger |c DE-627 |e rda | ||
041 | |a eng | ||
082 | 0 | 4 | |a 570 |a 610 |q DE-600 |
084 | |a 44.45 |2 bkl | ||
100 | 1 | |a Carvalho, Brener C. |e verfasserin |4 aut | |
245 | 1 | 0 | |a Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression |
264 | 1 | |c 2019 | |
336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. | ||
650 | 4 | |a Macrophage | |
650 | 4 | |a Toll-like receptor | |
650 | 4 | |a LPS | |
650 | 4 | |a Rap GTPase | |
650 | 4 | |a Rap2 | |
650 | 4 | |a NF-κB | |
700 | 1 | |a Oliveira, Leonardo C. |e verfasserin |0 (orcid)0000-0002-7393-5013 |4 aut | |
700 | 1 | |a Rocha, Carolina D. |e verfasserin |4 aut | |
700 | 1 | |a Fernandes, Heliana B. |e verfasserin |4 aut | |
700 | 1 | |a Oliveira, Isadora M. |e verfasserin |4 aut | |
700 | 1 | |a Leão, Felipe B. |e verfasserin |0 (orcid)0000-0002-4130-8998 |4 aut | |
700 | 1 | |a Valverde, Thalita M. |e verfasserin |4 aut | |
700 | 1 | |a Rego, Igor M.G. |e verfasserin |4 aut | |
700 | 1 | |a Ghosh, Sankar |e verfasserin |4 aut | |
700 | 1 | |a Silva, Aristóbolo M. |e verfasserin |0 (orcid)0000-0001-7473-7433 |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Molecular immunology |d Amsterdam [u.a.] : Elsevier, 1979 |g 109, Seite 27-37 |h Online-Ressource |w (DE-627)320511332 |w (DE-600)2013448-4 |w (DE-576)252776437 |x 1872-9142 |7 nnns |
773 | 1 | 8 | |g volume:109 |g pages:27-37 |
912 | |a GBV_USEFLAG_U | ||
912 | |a SYSFLAG_U | ||
912 | |a GBV_ELV | ||
912 | |a SSG-OLC-PHA | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_31 | ||
912 | |a GBV_ILN_32 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_70 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_90 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_100 | ||
912 | |a GBV_ILN_101 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_224 | ||
912 | |a GBV_ILN_370 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_702 | ||
912 | |a GBV_ILN_2004 | ||
912 | |a GBV_ILN_2005 | ||
912 | |a GBV_ILN_2025 | ||
912 | |a GBV_ILN_2034 | ||
912 | |a GBV_ILN_2044 | ||
912 | |a GBV_ILN_2048 | ||
912 | |a GBV_ILN_2049 | ||
912 | |a GBV_ILN_2050 | ||
912 | |a GBV_ILN_2056 | ||
912 | |a GBV_ILN_2059 | ||
912 | |a GBV_ILN_2061 | ||
912 | |a GBV_ILN_2064 | ||
912 | |a GBV_ILN_2068 | ||
912 | |a GBV_ILN_2111 | ||
912 | |a GBV_ILN_2113 | ||
912 | |a GBV_ILN_2129 | ||
912 | |a GBV_ILN_2143 | ||
912 | |a GBV_ILN_2153 | ||
912 | |a GBV_ILN_2336 | ||
912 | |a GBV_ILN_2522 | ||
912 | |a GBV_ILN_4251 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4326 | ||
912 | |a GBV_ILN_4333 | ||
912 | |a GBV_ILN_4334 | ||
912 | |a GBV_ILN_4335 | ||
936 | b | k | |a 44.45 |j Immunologie |
951 | |a AR | ||
952 | |d 109 |h 27-37 |
author_variant |
b c c bc bcc l c o lc lco c d r cd cdr h b f hb hbf i m o im imo f b l fb fbl t m v tm tmv i m r im imr s g sg a m s am ams |
---|---|
matchkey_str |
article:18729142:2019----::ohncdwadvrxrsinfa2saltaenarpaersliipimnonbcii |
hierarchy_sort_str |
2019 |
bklnumber |
44.45 |
publishDate |
2019 |
allfields |
10.1016/j.molimm.2019.02.015 doi (DE-627)ELV002032236 (ELSEVIER)S0161-5890(18)30761-2 DE-627 ger DE-627 rda eng 570 610 DE-600 44.45 bkl Carvalho, Brener C. verfasserin aut Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. Macrophage Toll-like receptor LPS Rap GTPase Rap2 NF-κB Oliveira, Leonardo C. verfasserin (orcid)0000-0002-7393-5013 aut Rocha, Carolina D. verfasserin aut Fernandes, Heliana B. verfasserin aut Oliveira, Isadora M. verfasserin aut Leão, Felipe B. verfasserin (orcid)0000-0002-4130-8998 aut Valverde, Thalita M. verfasserin aut Rego, Igor M.G. verfasserin aut Ghosh, Sankar verfasserin aut Silva, Aristóbolo M. verfasserin (orcid)0000-0001-7473-7433 aut Enthalten in Molecular immunology Amsterdam [u.a.] : Elsevier, 1979 109, Seite 27-37 Online-Ressource (DE-627)320511332 (DE-600)2013448-4 (DE-576)252776437 1872-9142 nnns volume:109 pages:27-37 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_2522 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 44.45 Immunologie AR 109 27-37 |
spelling |
10.1016/j.molimm.2019.02.015 doi (DE-627)ELV002032236 (ELSEVIER)S0161-5890(18)30761-2 DE-627 ger DE-627 rda eng 570 610 DE-600 44.45 bkl Carvalho, Brener C. verfasserin aut Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. Macrophage Toll-like receptor LPS Rap GTPase Rap2 NF-κB Oliveira, Leonardo C. verfasserin (orcid)0000-0002-7393-5013 aut Rocha, Carolina D. verfasserin aut Fernandes, Heliana B. verfasserin aut Oliveira, Isadora M. verfasserin aut Leão, Felipe B. verfasserin (orcid)0000-0002-4130-8998 aut Valverde, Thalita M. verfasserin aut Rego, Igor M.G. verfasserin aut Ghosh, Sankar verfasserin aut Silva, Aristóbolo M. verfasserin (orcid)0000-0001-7473-7433 aut Enthalten in Molecular immunology Amsterdam [u.a.] : Elsevier, 1979 109, Seite 27-37 Online-Ressource (DE-627)320511332 (DE-600)2013448-4 (DE-576)252776437 1872-9142 nnns volume:109 pages:27-37 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_2522 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 44.45 Immunologie AR 109 27-37 |
allfields_unstemmed |
10.1016/j.molimm.2019.02.015 doi (DE-627)ELV002032236 (ELSEVIER)S0161-5890(18)30761-2 DE-627 ger DE-627 rda eng 570 610 DE-600 44.45 bkl Carvalho, Brener C. verfasserin aut Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. Macrophage Toll-like receptor LPS Rap GTPase Rap2 NF-κB Oliveira, Leonardo C. verfasserin (orcid)0000-0002-7393-5013 aut Rocha, Carolina D. verfasserin aut Fernandes, Heliana B. verfasserin aut Oliveira, Isadora M. verfasserin aut Leão, Felipe B. verfasserin (orcid)0000-0002-4130-8998 aut Valverde, Thalita M. verfasserin aut Rego, Igor M.G. verfasserin aut Ghosh, Sankar verfasserin aut Silva, Aristóbolo M. verfasserin (orcid)0000-0001-7473-7433 aut Enthalten in Molecular immunology Amsterdam [u.a.] : Elsevier, 1979 109, Seite 27-37 Online-Ressource (DE-627)320511332 (DE-600)2013448-4 (DE-576)252776437 1872-9142 nnns volume:109 pages:27-37 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_2522 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 44.45 Immunologie AR 109 27-37 |
allfieldsGer |
10.1016/j.molimm.2019.02.015 doi (DE-627)ELV002032236 (ELSEVIER)S0161-5890(18)30761-2 DE-627 ger DE-627 rda eng 570 610 DE-600 44.45 bkl Carvalho, Brener C. verfasserin aut Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. Macrophage Toll-like receptor LPS Rap GTPase Rap2 NF-κB Oliveira, Leonardo C. verfasserin (orcid)0000-0002-7393-5013 aut Rocha, Carolina D. verfasserin aut Fernandes, Heliana B. verfasserin aut Oliveira, Isadora M. verfasserin aut Leão, Felipe B. verfasserin (orcid)0000-0002-4130-8998 aut Valverde, Thalita M. verfasserin aut Rego, Igor M.G. verfasserin aut Ghosh, Sankar verfasserin aut Silva, Aristóbolo M. verfasserin (orcid)0000-0001-7473-7433 aut Enthalten in Molecular immunology Amsterdam [u.a.] : Elsevier, 1979 109, Seite 27-37 Online-Ressource (DE-627)320511332 (DE-600)2013448-4 (DE-576)252776437 1872-9142 nnns volume:109 pages:27-37 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_2522 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 44.45 Immunologie AR 109 27-37 |
allfieldsSound |
10.1016/j.molimm.2019.02.015 doi (DE-627)ELV002032236 (ELSEVIER)S0161-5890(18)30761-2 DE-627 ger DE-627 rda eng 570 610 DE-600 44.45 bkl Carvalho, Brener C. verfasserin aut Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression 2019 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. Macrophage Toll-like receptor LPS Rap GTPase Rap2 NF-κB Oliveira, Leonardo C. verfasserin (orcid)0000-0002-7393-5013 aut Rocha, Carolina D. verfasserin aut Fernandes, Heliana B. verfasserin aut Oliveira, Isadora M. verfasserin aut Leão, Felipe B. verfasserin (orcid)0000-0002-4130-8998 aut Valverde, Thalita M. verfasserin aut Rego, Igor M.G. verfasserin aut Ghosh, Sankar verfasserin aut Silva, Aristóbolo M. verfasserin (orcid)0000-0001-7473-7433 aut Enthalten in Molecular immunology Amsterdam [u.a.] : Elsevier, 1979 109, Seite 27-37 Online-Ressource (DE-627)320511332 (DE-600)2013448-4 (DE-576)252776437 1872-9142 nnns volume:109 pages:27-37 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_2522 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 44.45 Immunologie AR 109 27-37 |
language |
English |
source |
Enthalten in Molecular immunology 109, Seite 27-37 volume:109 pages:27-37 |
sourceStr |
Enthalten in Molecular immunology 109, Seite 27-37 volume:109 pages:27-37 |
format_phy_str_mv |
Article |
bklname |
Immunologie |
institution |
findex.gbv.de |
topic_facet |
Macrophage Toll-like receptor LPS Rap GTPase Rap2 NF-κB |
dewey-raw |
570 |
isfreeaccess_bool |
false |
container_title |
Molecular immunology |
authorswithroles_txt_mv |
Carvalho, Brener C. @@aut@@ Oliveira, Leonardo C. @@aut@@ Rocha, Carolina D. @@aut@@ Fernandes, Heliana B. @@aut@@ Oliveira, Isadora M. @@aut@@ Leão, Felipe B. @@aut@@ Valverde, Thalita M. @@aut@@ Rego, Igor M.G. @@aut@@ Ghosh, Sankar @@aut@@ Silva, Aristóbolo M. @@aut@@ |
publishDateDaySort_date |
2019-01-01T00:00:00Z |
hierarchy_top_id |
320511332 |
dewey-sort |
3570 |
id |
ELV002032236 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV002032236</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230524165102.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230429s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.molimm.2019.02.015</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV002032236</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0161-5890(18)30761-2</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="a">610</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.45</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Carvalho, Brener C.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Macrophage</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Toll-like receptor</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">LPS</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rap GTPase</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rap2</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">NF-κB</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Oliveira, Leonardo C.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-7393-5013</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rocha, Carolina D.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fernandes, Heliana B.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Oliveira, Isadora M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Leão, Felipe B.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-4130-8998</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Valverde, Thalita M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rego, Igor M.G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ghosh, Sankar</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Silva, Aristóbolo M.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0001-7473-7433</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Molecular immunology</subfield><subfield code="d">Amsterdam [u.a.] : Elsevier, 1979</subfield><subfield code="g">109, Seite 27-37</subfield><subfield code="h">Online-Ressource</subfield><subfield code="w">(DE-627)320511332</subfield><subfield code="w">(DE-600)2013448-4</subfield><subfield code="w">(DE-576)252776437</subfield><subfield code="x">1872-9142</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:109</subfield><subfield code="g">pages:27-37</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_32</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_90</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_101</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2004</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2025</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2034</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2044</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2048</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2049</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2050</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2056</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2059</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2061</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2064</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2068</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2113</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2129</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2143</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2153</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2522</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4251</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4326</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4333</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4334</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4335</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.45</subfield><subfield code="j">Immunologie</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">109</subfield><subfield code="h">27-37</subfield></datafield></record></collection>
|
author |
Carvalho, Brener C. |
spellingShingle |
Carvalho, Brener C. ddc 570 bkl 44.45 misc Macrophage misc Toll-like receptor misc LPS misc Rap GTPase misc Rap2 misc NF-κB Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression |
authorStr |
Carvalho, Brener C. |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)320511332 |
format |
electronic Article |
dewey-ones |
570 - Life sciences; biology 610 - Medicine & health |
delete_txt_mv |
keep |
author_role |
aut aut aut aut aut aut aut aut aut aut |
collection |
elsevier |
remote_str |
true |
illustrated |
Not Illustrated |
issn |
1872-9142 |
topic_title |
570 610 DE-600 44.45 bkl Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression Macrophage Toll-like receptor LPS Rap GTPase Rap2 NF-κB |
topic |
ddc 570 bkl 44.45 misc Macrophage misc Toll-like receptor misc LPS misc Rap GTPase misc Rap2 misc NF-κB |
topic_unstemmed |
ddc 570 bkl 44.45 misc Macrophage misc Toll-like receptor misc LPS misc Rap GTPase misc Rap2 misc NF-κB |
topic_browse |
ddc 570 bkl 44.45 misc Macrophage misc Toll-like receptor misc LPS misc Rap GTPase misc Rap2 misc NF-κB |
format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
cr |
hierarchy_parent_title |
Molecular immunology |
hierarchy_parent_id |
320511332 |
dewey-tens |
570 - Life sciences; biology 610 - Medicine & health |
hierarchy_top_title |
Molecular immunology |
isfreeaccess_txt |
false |
familylinks_str_mv |
(DE-627)320511332 (DE-600)2013448-4 (DE-576)252776437 |
title |
Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression |
ctrlnum |
(DE-627)ELV002032236 (ELSEVIER)S0161-5890(18)30761-2 |
title_full |
Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression |
author_sort |
Carvalho, Brener C. |
journal |
Molecular immunology |
journalStr |
Molecular immunology |
lang_code |
eng |
isOA_bool |
false |
dewey-hundreds |
500 - Science 600 - Technology |
recordtype |
marc |
publishDateSort |
2019 |
contenttype_str_mv |
zzz |
container_start_page |
27 |
author_browse |
Carvalho, Brener C. Oliveira, Leonardo C. Rocha, Carolina D. Fernandes, Heliana B. Oliveira, Isadora M. Leão, Felipe B. Valverde, Thalita M. Rego, Igor M.G. Ghosh, Sankar Silva, Aristóbolo M. |
container_volume |
109 |
class |
570 610 DE-600 44.45 bkl |
format_se |
Elektronische Aufsätze |
author-letter |
Carvalho, Brener C. |
doi_str_mv |
10.1016/j.molimm.2019.02.015 |
normlink |
(ORCID)0000-0002-7393-5013 (ORCID)0000-0002-4130-8998 (ORCID)0000-0001-7473-7433 |
normlink_prefix_str_mv |
(orcid)0000-0002-7393-5013 (orcid)0000-0002-4130-8998 (orcid)0000-0001-7473-7433 |
dewey-full |
570 610 |
author2-role |
verfasserin |
title_sort |
both knock-down and overexpression of rap2a small gtpase in macrophages result in impairment of nf-κb activity and inflammatory gene expression |
title_auth |
Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression |
abstract |
Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. |
abstractGer |
Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. |
abstract_unstemmed |
Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages. |
collection_details |
GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2336 GBV_ILN_2522 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 |
title_short |
Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression |
remote_bool |
true |
author2 |
Oliveira, Leonardo C. Rocha, Carolina D. Fernandes, Heliana B. Oliveira, Isadora M. Leão, Felipe B. Valverde, Thalita M. Rego, Igor M.G. Ghosh, Sankar Silva, Aristóbolo M. |
author2Str |
Oliveira, Leonardo C. Rocha, Carolina D. Fernandes, Heliana B. Oliveira, Isadora M. Leão, Felipe B. Valverde, Thalita M. Rego, Igor M.G. Ghosh, Sankar Silva, Aristóbolo M. |
ppnlink |
320511332 |
mediatype_str_mv |
c |
isOA_txt |
false |
hochschulschrift_bool |
false |
doi_str |
10.1016/j.molimm.2019.02.015 |
up_date |
2024-07-06T23:23:16.982Z |
_version_ |
1803873887960694784 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV002032236</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230524165102.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230429s2019 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.molimm.2019.02.015</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV002032236</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0161-5890(18)30761-2</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="a">610</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.45</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Carvalho, Brener C.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Macrophage</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Toll-like receptor</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">LPS</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rap GTPase</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rap2</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">NF-κB</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Oliveira, Leonardo C.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-7393-5013</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rocha, Carolina D.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Fernandes, Heliana B.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Oliveira, Isadora M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Leão, Felipe B.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0002-4130-8998</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Valverde, Thalita M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rego, Igor M.G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ghosh, Sankar</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Silva, Aristóbolo M.</subfield><subfield code="e">verfasserin</subfield><subfield code="0">(orcid)0000-0001-7473-7433</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Molecular immunology</subfield><subfield code="d">Amsterdam [u.a.] : Elsevier, 1979</subfield><subfield code="g">109, Seite 27-37</subfield><subfield code="h">Online-Ressource</subfield><subfield code="w">(DE-627)320511332</subfield><subfield code="w">(DE-600)2013448-4</subfield><subfield code="w">(DE-576)252776437</subfield><subfield code="x">1872-9142</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:109</subfield><subfield code="g">pages:27-37</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_32</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_90</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_101</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2004</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2025</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2034</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2044</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2048</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2049</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2050</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2056</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2059</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2061</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2064</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2068</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2113</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2129</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2143</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2153</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2336</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2522</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4251</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4326</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4333</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4334</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4335</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.45</subfield><subfield code="j">Immunologie</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">109</subfield><subfield code="h">27-37</subfield></datafield></record></collection>
|
score |
7.3989954 |