NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes

Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibi...
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Gespeichert in:

Autor*in:	Guo, Yiyan [verfasserIn] Jin, Liping [verfasserIn] Dong, Liang [verfasserIn] Zhang, Mi [verfasserIn] Kuang, Yehong [verfasserIn] Chen, Xiang [verfasserIn] Zhu, Wu [verfasserIn] Yin, Mingzhu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	RIPK1 NF-κB TLR1 Keratinocytes Psoriasis

Übergeordnetes Werk:	Enthalten in: Biomedicine & pharmacotherapy - Amsterdam [u.a.] : Elsevier Science, 1989, 162
Übergeordnetes Werk:	volume:162

DOI / URN:	10.1016/j.biopha.2023.114638

Katalog-ID:	ELV00982376X

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245	1	0	\|a NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes
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520			\|a Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis.
650		4	\|a RIPK1
650		4	\|a NF-κB
650		4	\|a TLR1
650		4	\|a Keratinocytes
650		4	\|a Psoriasis
700	1		\|a Jin, Liping \|e verfasserin \|4 aut
700	1		\|a Dong, Liang \|e verfasserin \|4 aut
700	1		\|a Zhang, Mi \|e verfasserin \|4 aut
700	1		\|a Kuang, Yehong \|e verfasserin \|4 aut
700	1		\|a Chen, Xiang \|e verfasserin \|4 aut
700	1		\|a Zhu, Wu \|e verfasserin \|4 aut
700	1		\|a Yin, Mingzhu \|e verfasserin \|0 (orcid)0000-0002-6964-7131 \|4 aut
773	0	8	\|i Enthalten in \|t Biomedicine & pharmacotherapy \|d Amsterdam [u.a.] : Elsevier Science, 1989 \|g 162 \|h Online-Ressource \|w (DE-627)306717565 \|w (DE-600)1501510-5 \|w (DE-576)261593021 \|x 1950-6007 \|7 nnns
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912			\|a GBV_ILN_39
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912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
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912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
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912			\|a GBV_ILN_165
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912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
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912			\|a GBV_ILN_285
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912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2008
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
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912			\|a GBV_ILN_2232
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
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Indexfelder

author_variant	y g yg l j lj l d ld m z mz y k yk x c xc w z wz m y my
matchkey_str	article:19506007:2023----::hd02mloaeifamtoadrlfrtobteiknbl1xs
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bklnumber	44.40
publishDate	2023
allfields	10.1016/j.biopha.2023.114638 doi (DE-627)ELV00982376X (ELSEVIER)S0753-3322(23)00426-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Guo, Yiyan verfasserin aut NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis. RIPK1 NF-κB TLR1 Keratinocytes Psoriasis Jin, Liping verfasserin aut Dong, Liang verfasserin aut Zhang, Mi verfasserin aut Kuang, Yehong verfasserin aut Chen, Xiang verfasserin aut Zhu, Wu verfasserin aut Yin, Mingzhu verfasserin (orcid)0000-0002-6964-7131 aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 162 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:162 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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 44.40 Pharmazie Pharmazeutika VZ AR 162
spelling	10.1016/j.biopha.2023.114638 doi (DE-627)ELV00982376X (ELSEVIER)S0753-3322(23)00426-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Guo, Yiyan verfasserin aut NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis. RIPK1 NF-κB TLR1 Keratinocytes Psoriasis Jin, Liping verfasserin aut Dong, Liang verfasserin aut Zhang, Mi verfasserin aut Kuang, Yehong verfasserin aut Chen, Xiang verfasserin aut Zhu, Wu verfasserin aut Yin, Mingzhu verfasserin (orcid)0000-0002-6964-7131 aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 162 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:162 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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 44.40 Pharmazie Pharmazeutika VZ AR 162
allfields_unstemmed	10.1016/j.biopha.2023.114638 doi (DE-627)ELV00982376X (ELSEVIER)S0753-3322(23)00426-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Guo, Yiyan verfasserin aut NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis. RIPK1 NF-κB TLR1 Keratinocytes Psoriasis Jin, Liping verfasserin aut Dong, Liang verfasserin aut Zhang, Mi verfasserin aut Kuang, Yehong verfasserin aut Chen, Xiang verfasserin aut Zhu, Wu verfasserin aut Yin, Mingzhu verfasserin (orcid)0000-0002-6964-7131 aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 162 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:162 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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 44.40 Pharmazie Pharmazeutika VZ AR 162
allfieldsGer	10.1016/j.biopha.2023.114638 doi (DE-627)ELV00982376X (ELSEVIER)S0753-3322(23)00426-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Guo, Yiyan verfasserin aut NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis. RIPK1 NF-κB TLR1 Keratinocytes Psoriasis Jin, Liping verfasserin aut Dong, Liang verfasserin aut Zhang, Mi verfasserin aut Kuang, Yehong verfasserin aut Chen, Xiang verfasserin aut Zhu, Wu verfasserin aut Yin, Mingzhu verfasserin (orcid)0000-0002-6964-7131 aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 162 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:162 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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 44.40 Pharmazie Pharmazeutika VZ AR 162
allfieldsSound	10.1016/j.biopha.2023.114638 doi (DE-627)ELV00982376X (ELSEVIER)S0753-3322(23)00426-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Guo, Yiyan verfasserin aut NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis. RIPK1 NF-κB TLR1 Keratinocytes Psoriasis Jin, Liping verfasserin aut Dong, Liang verfasserin aut Zhang, Mi verfasserin aut Kuang, Yehong verfasserin aut Chen, Xiang verfasserin aut Zhu, Wu verfasserin aut Yin, Mingzhu verfasserin (orcid)0000-0002-6964-7131 aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 162 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:162 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 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 44.40 Pharmazie Pharmazeutika VZ AR 162
language	English
source	Enthalten in Biomedicine & pharmacotherapy 162 volume:162
sourceStr	Enthalten in Biomedicine & pharmacotherapy 162 volume:162
format_phy_str_mv	Article
bklname	Pharmazie Pharmazeutika
institution	findex.gbv.de
topic_facet	RIPK1 NF-κB TLR1 Keratinocytes Psoriasis
dewey-raw	610
isfreeaccess_bool	false
container_title	Biomedicine & pharmacotherapy
authorswithroles_txt_mv	Guo, Yiyan @@aut@@ Jin, Liping @@aut@@ Dong, Liang @@aut@@ Zhang, Mi @@aut@@ Kuang, Yehong @@aut@@ Chen, Xiang @@aut@@ Zhu, Wu @@aut@@ Yin, Mingzhu @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	306717565
dewey-sort	3610
id	ELV00982376X
language_de	englisch
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author	Guo, Yiyan
spellingShingle	Guo, Yiyan ddc 610 bkl 44.40 misc RIPK1 misc NF-κB misc TLR1 misc Keratinocytes misc Psoriasis NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes
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topic_title	610 VZ 44.40 bkl NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes RIPK1 NF-κB TLR1 Keratinocytes Psoriasis
topic	ddc 610 bkl 44.40 misc RIPK1 misc NF-κB misc TLR1 misc Keratinocytes misc Psoriasis
topic_unstemmed	ddc 610 bkl 44.40 misc RIPK1 misc NF-κB misc TLR1 misc Keratinocytes misc Psoriasis
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title	NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes
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title_full	NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes
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journal	Biomedicine & pharmacotherapy
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author_browse	Guo, Yiyan Jin, Liping Dong, Liang Zhang, Mi Kuang, Yehong Chen, Xiang Zhu, Wu Yin, Mingzhu
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title_sort	nhwd-1062 ameliorates inflammation and proliferation by the ripk1/nf-κb/tlr1 axis in psoriatic keratinocytes
title_auth	NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes
abstract	Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis.
abstractGer	Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis.
abstract_unstemmed	Psoriasis is a common chronic inflammatory skin disease. RIPK1 plays an important role in inflammatory diseases. At present, the clinical efficacy of the RIPK1 inhibitor is limited and the regulatory mechanism is unclear in the treatment of psoriasis. Therefore, our team developed a new RIPK1 inhibitor, NHWD-1062, which showed a slightly lower IC50 in U937 cells than that of GSK’772 (a RIPK1 inhibitor in clinical trials) (11 nM vs. 14 nM), indicating that the new RIPK1 inhibitor was no less inhibitory than GSK’772. In this study, we evaluated the therapeutic effects of NHWD-1062 using an IMQ-induced mouse model of psoriasis and explored the precise regulatory mechanism involved. We found that gavage of NHWD-1062 significantly ameliorated the inflammatory response and inhibited the abnormal proliferation of the epidermis in IMQ-induced psoriatic mice. We then elucidated the mechanism of NHWD-1062, which was that suppressed the proliferation and inflammation of keratinocytes in vitro and in vivo through the RIPK1/NF-κB/TLR1 axis. Dual-luciferase reporter assay indicated that P65 can directly target the TLR1 promoter region and activate TLR1 expression, leading to inflammation. In summary, our study demonstrates that NHWD-1062 alleviates psoriasis-like inflammation by inhibiting the activation of the RIPK1/NF-κB/TLR1 axis, which has not been previously reported and further provides evidence for the clinical translation of NHWD-1062 in the treatment of psoriasis.
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title_short	NHWD-1062 ameliorates inflammation and proliferation by the RIPK1/NF-κB/TLR1 axis in Psoriatic Keratinocytes
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author2	Jin, Liping Dong, Liang Zhang, Mi Kuang, Yehong Chen, Xiang Zhu, Wu Yin, Mingzhu
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doi_str	10.1016/j.biopha.2023.114638
up_date	2024-07-07T00:28:36.286Z
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