MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs

Chronic liver disease mediated by the activation of hepatic stellate cells (HSCs) leads to liver fibrosis. The signal adaptor MyD88 of Toll-like receptor (TLR) signaling is involved during the progression of liver fibrosis. However, the specific role of MyD88 in myeloid cells in liver fibrosis has n...

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Autores principales:	Shuang Ge, Wei Yang, Haiqiang Chen, Qi Yuan, Shi Liu, Yongxiang Zhao, Jinhua Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MyD88 macrophage HSC liver fibrosis NLRP3 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5d9f32eb73414c6a9e08c88c69a57f69
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spelling	oai:doaj.org-article:5d9f32eb73414c6a9e08c88c69a57f692021-11-25T17:56:25ZMyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs10.3390/ijms2222124131422-00671661-6596https://doaj.org/article/5d9f32eb73414c6a9e08c88c69a57f692021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12413https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Chronic liver disease mediated by the activation of hepatic stellate cells (HSCs) leads to liver fibrosis. The signal adaptor MyD88 of Toll-like receptor (TLR) signaling is involved during the progression of liver fibrosis. However, the specific role of MyD88 in myeloid cells in liver fibrosis has not been thoroughly investigated. In this study, we used a carbon tetrachloride (CCl<sub>4</sub>)-induced mouse fibrosis model in which MyD88 was selectively depleted in myeloid cells. MyD88 deficiency in myeloid cells attenuated liver fibrosis in mice and decreased inflammatory cell infiltration. Furthermore, deficiency of MyD88 in macrophages inhibits the secretion of CXC motif chemokine 2 (CXCL2), which restrains the activation of HSCs characterized by NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation. Moreover, targeting CXCL2 by CXCR2 inhibitors attenuated the activation of HSCs and reduced liver fibrosis. Thus, MyD88 may represent a potential candidate target for the prevention and treatment of liver fibrosis.Shuang GeWei YangHaiqiang ChenQi YuanShi LiuYongxiang ZhaoJinhua ZhangMDPI AGarticleMyD88macrophageHSCliver fibrosisNLRP3Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12413, p 12413 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MyD88 macrophage HSC liver fibrosis NLRP3 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	MyD88 macrophage HSC liver fibrosis NLRP3 Biology (General) QH301-705.5 Chemistry QD1-999 Shuang Ge Wei Yang Haiqiang Chen Qi Yuan Shi Liu Yongxiang Zhao Jinhua Zhang MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs
description	Chronic liver disease mediated by the activation of hepatic stellate cells (HSCs) leads to liver fibrosis. The signal adaptor MyD88 of Toll-like receptor (TLR) signaling is involved during the progression of liver fibrosis. However, the specific role of MyD88 in myeloid cells in liver fibrosis has not been thoroughly investigated. In this study, we used a carbon tetrachloride (CCl<sub>4</sub>)-induced mouse fibrosis model in which MyD88 was selectively depleted in myeloid cells. MyD88 deficiency in myeloid cells attenuated liver fibrosis in mice and decreased inflammatory cell infiltration. Furthermore, deficiency of MyD88 in macrophages inhibits the secretion of CXC motif chemokine 2 (CXCL2), which restrains the activation of HSCs characterized by NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation. Moreover, targeting CXCL2 by CXCR2 inhibitors attenuated the activation of HSCs and reduced liver fibrosis. Thus, MyD88 may represent a potential candidate target for the prevention and treatment of liver fibrosis.
format	article
author	Shuang Ge Wei Yang Haiqiang Chen Qi Yuan Shi Liu Yongxiang Zhao Jinhua Zhang
author_facet	Shuang Ge Wei Yang Haiqiang Chen Qi Yuan Shi Liu Yongxiang Zhao Jinhua Zhang
author_sort	Shuang Ge
title	MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs
title_short	MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs
title_full	MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs
title_fullStr	MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs
title_full_unstemmed	MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs
title_sort	myd88 in macrophages enhances liver fibrosis by activation of nlrp3 inflammasome in hscs
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5d9f32eb73414c6a9e08c88c69a57f69
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MyD88 in Macrophages Enhances Liver Fibrosis by Activation of NLRP3 Inflammasome in HSCs

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