期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 22, 页码 -出版社
MDPI
DOI: 10.3390/ijms222212413
关键词
MyD88; macrophage; HSC; liver fibrosis; NLRP3
资金
- Ministry of Science and Technology of China [2015CB553705]
- National Natural Science Foundation of China [81972689, 81772497]
Deficiency of MyD88 in myeloid cells attenuates liver fibrosis and reduces inflammatory cell infiltration, possibly through inhibiting the secretion of CXCL2. Targeting CXCL2 using CXCR2 inhibitors can also reduce liver fibrosis. MyD88 may be a potential target for the prevention and treatment of liver fibrosis.
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 (CCl4)-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.
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