Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway

Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Li Wang [verfasserIn] Dong-Sheng Zhai [verfasserIn] Ban-Jun Ruan [verfasserIn] Cheng-Ming Xu [verfasserIn] Zi-Chen Ye [verfasserIn] Huan-Yu Lu [verfasserIn] Ying-Hao Jiang [verfasserIn] Zhen-Yu Wang [verfasserIn] An Xiang [verfasserIn] Yuan Yang [verfasserIn] Jian-Lin Yuan [verfasserIn] Zi-Fan Lu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	quaking macrophage polarization endotoxemia aryl hydrocarbon receptor NF-κB

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 8(2017)
Übergeordnetes Werk:	volume:8 ; year:2017

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2017.01754

Katalog-ID:	DOAJ010987266

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allfields	10.3389/fimmu.2017.01754 doi (DE-627)DOAJ010987266 (DE-599)DOAJd8acc36627f44228949d6564b5f38ca0 DE-627 ger DE-627 rakwb eng RC581-607 Li Wang verfasserin aut Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway. quaking macrophage polarization endotoxemia aryl hydrocarbon receptor NF-κB Immunologic diseases. Allergy Dong-Sheng Zhai verfasserin aut Ban-Jun Ruan verfasserin aut Cheng-Ming Xu verfasserin aut Zi-Chen Ye verfasserin aut Huan-Yu Lu verfasserin aut Ying-Hao Jiang verfasserin aut Zhen-Yu Wang verfasserin aut An Xiang verfasserin aut Yuan Yang verfasserin aut Jian-Lin Yuan verfasserin aut Zi-Fan Lu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01754 kostenfrei https://doaj.org/article/d8acc36627f44228949d6564b5f38ca0 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01754/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017
spelling	10.3389/fimmu.2017.01754 doi (DE-627)DOAJ010987266 (DE-599)DOAJd8acc36627f44228949d6564b5f38ca0 DE-627 ger DE-627 rakwb eng RC581-607 Li Wang verfasserin aut Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway. quaking macrophage polarization endotoxemia aryl hydrocarbon receptor NF-κB Immunologic diseases. Allergy Dong-Sheng Zhai verfasserin aut Ban-Jun Ruan verfasserin aut Cheng-Ming Xu verfasserin aut Zi-Chen Ye verfasserin aut Huan-Yu Lu verfasserin aut Ying-Hao Jiang verfasserin aut Zhen-Yu Wang verfasserin aut An Xiang verfasserin aut Yuan Yang verfasserin aut Jian-Lin Yuan verfasserin aut Zi-Fan Lu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01754 kostenfrei https://doaj.org/article/d8acc36627f44228949d6564b5f38ca0 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01754/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017
allfields_unstemmed	10.3389/fimmu.2017.01754 doi (DE-627)DOAJ010987266 (DE-599)DOAJd8acc36627f44228949d6564b5f38ca0 DE-627 ger DE-627 rakwb eng RC581-607 Li Wang verfasserin aut Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway. quaking macrophage polarization endotoxemia aryl hydrocarbon receptor NF-κB Immunologic diseases. Allergy Dong-Sheng Zhai verfasserin aut Ban-Jun Ruan verfasserin aut Cheng-Ming Xu verfasserin aut Zi-Chen Ye verfasserin aut Huan-Yu Lu verfasserin aut Ying-Hao Jiang verfasserin aut Zhen-Yu Wang verfasserin aut An Xiang verfasserin aut Yuan Yang verfasserin aut Jian-Lin Yuan verfasserin aut Zi-Fan Lu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01754 kostenfrei https://doaj.org/article/d8acc36627f44228949d6564b5f38ca0 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01754/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017
allfieldsGer	10.3389/fimmu.2017.01754 doi (DE-627)DOAJ010987266 (DE-599)DOAJd8acc36627f44228949d6564b5f38ca0 DE-627 ger DE-627 rakwb eng RC581-607 Li Wang verfasserin aut Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway. quaking macrophage polarization endotoxemia aryl hydrocarbon receptor NF-κB Immunologic diseases. Allergy Dong-Sheng Zhai verfasserin aut Ban-Jun Ruan verfasserin aut Cheng-Ming Xu verfasserin aut Zi-Chen Ye verfasserin aut Huan-Yu Lu verfasserin aut Ying-Hao Jiang verfasserin aut Zhen-Yu Wang verfasserin aut An Xiang verfasserin aut Yuan Yang verfasserin aut Jian-Lin Yuan verfasserin aut Zi-Fan Lu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01754 kostenfrei https://doaj.org/article/d8acc36627f44228949d6564b5f38ca0 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01754/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017
allfieldsSound	10.3389/fimmu.2017.01754 doi (DE-627)DOAJ010987266 (DE-599)DOAJd8acc36627f44228949d6564b5f38ca0 DE-627 ger DE-627 rakwb eng RC581-607 Li Wang verfasserin aut Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway. quaking macrophage polarization endotoxemia aryl hydrocarbon receptor NF-κB Immunologic diseases. Allergy Dong-Sheng Zhai verfasserin aut Ban-Jun Ruan verfasserin aut Cheng-Ming Xu verfasserin aut Zi-Chen Ye verfasserin aut Huan-Yu Lu verfasserin aut Ying-Hao Jiang verfasserin aut Zhen-Yu Wang verfasserin aut An Xiang verfasserin aut Yuan Yang verfasserin aut Jian-Lin Yuan verfasserin aut Zi-Fan Lu verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 8(2017) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:8 year:2017 https://doi.org/10.3389/fimmu.2017.01754 kostenfrei https://doaj.org/article/d8acc36627f44228949d6564b5f38ca0 kostenfrei http://journal.frontiersin.org/article/10.3389/fimmu.2017.01754/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2017
language	English
source	In Frontiers in Immunology 8(2017) volume:8 year:2017
sourceStr	In Frontiers in Immunology 8(2017) volume:8 year:2017
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	quaking macrophage polarization endotoxemia aryl hydrocarbon receptor NF-κB Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Li Wang @@aut@@ Dong-Sheng Zhai @@aut@@ Ban-Jun Ruan @@aut@@ Cheng-Ming Xu @@aut@@ Zi-Chen Ye @@aut@@ Huan-Yu Lu @@aut@@ Ying-Hao Jiang @@aut@@ Zhen-Yu Wang @@aut@@ An Xiang @@aut@@ Yuan Yang @@aut@@ Jian-Lin Yuan @@aut@@ Zi-Fan Lu @@aut@@
publishDateDaySort_date	2017-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ010987266
language_de	englisch
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callnumber-first	R - Medicine
author	Li Wang
spellingShingle	Li Wang misc RC581-607 misc quaking misc macrophage polarization misc endotoxemia misc aryl hydrocarbon receptor misc NF-κB misc Immunologic diseases. Allergy Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway
authorStr	Li Wang
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topic_title	RC581-607 Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway quaking macrophage polarization endotoxemia aryl hydrocarbon receptor NF-κB
topic	misc RC581-607 misc quaking misc macrophage polarization misc endotoxemia misc aryl hydrocarbon receptor misc NF-κB misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc quaking misc macrophage polarization misc endotoxemia misc aryl hydrocarbon receptor misc NF-κB misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc quaking misc macrophage polarization misc endotoxemia misc aryl hydrocarbon receptor misc NF-κB misc Immunologic diseases. Allergy
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title	Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway
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title_full	Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway
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author_browse	Li Wang Dong-Sheng Zhai Ban-Jun Ruan Cheng-Ming Xu Zi-Chen Ye Huan-Yu Lu Ying-Hao Jiang Zhen-Yu Wang An Xiang Yuan Yang Jian-Lin Yuan Zi-Fan Lu
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title_sort	quaking deficiency amplifies inflammation in experimental endotoxemia via the aryl hydrocarbon receptor/signal transducer and activator of transcription 1–nf-κb pathway
callnumber	RC581-607
title_auth	Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway
abstract	Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway.
abstractGer	Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway.
abstract_unstemmed	Macrophages, characterized by considerable diversity and plasticity, play a crucial role in a broad spectrum of biological processes, including inflammation. However, the molecular mechanisms underlying the diverse phenotypes of macrophages are not well defined. Here, we show that the RNA-binding protein, quaking (QKI), dynamically modulates macrophage polarization states. After lipopolysaccharide (LPS) stimulation, QKI-silenced RAW 264.7 cells displayed a pro-inflammatory M1 phenotype characterized by increased expression of iNOS, TNF-α, and IL-6 and decreased expression of anti-inflammatory factors, such as IL-10, found in inflammatory zone (Fizz1), and chitinase-like 3 (Chil3 or Ym1). By contrast, QKI5 overexpression led to a suppressive phenotype resembling M2 macrophages, even under M1 differentiation conditions. Moreover, myeloid-specific QKI-deficient mice tended to be more susceptible to LPS-induced endotoxic shock, while the exogenous transfer of macrophages overexpressing QKI5 exerted a significant improving effect. This improvement corresponded to a higher proportion of M2 macrophages, in line with elevated levels of IL-10, and a decrease in levels of pro-inflammatory mediators, such as IL-6, TNF-α, and IL-1β. Further mechanistic studies disclosed that QKI was a potent inhibitor of the nuclear factor-kappa B (NF-κB) pathway, suppressing p65 expression and phosphorylation. Strikingly, reduced expression of the aryl hydrocarbon receptor (Ahr) and reduced phosphorylation of signal transducer and activator of transcription 1 in QKI-deficient cells failed to restrain the transcriptional activity of NF-κB and NRL pyrin domain containing 3 (NLRP3) activation, while restoring QKI expression skewed the above M1-like response toward an anti-inflammatory M2 state. Taken together, these findings suggest a role for QKI in restraining overt innate immune responses by regulating the Ahr/STAT1–NF-κB pathway.
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title_short	Quaking Deficiency Amplifies Inflammation in Experimental Endotoxemia via the Aryl Hydrocarbon Receptor/Signal Transducer and Activator of Transcription 1–NF-κB Pathway
url	https://doi.org/10.3389/fimmu.2017.01754 https://doaj.org/article/d8acc36627f44228949d6564b5f38ca0 http://journal.frontiersin.org/article/10.3389/fimmu.2017.01754/full https://doaj.org/toc/1664-3224
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up_date	2024-07-03T17:51:31.146Z
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