期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 26, 期 22, 页码 5690-5701出版社
WILEY
DOI: 10.1111/jcmm.17599
关键词
autoimmune hepatitis; inflammation; macrophage receptor with collagenous structure; polyguanine
资金
- Foundation of Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Disease [2020E10014-002]
- Medicine Health Project of Zhejiang Province, China [2020KY276]
- National Natural Science Foundation of China [81770585, 82070593]
- Wenzhou Municipal Science and Technology Bureau [ZY2019008]
- Youth Science and Technology Innovation Cultivation Fund of Peking University School of Medicine [BMU2020PYB005]
- Zhejiang Provincial Natural Science Foundation of China [LD21H030002, LY21H030004]
This study investigated the role of MARCO and PolyG in the development and treatment of AIH. The results showed that treatment with PolyG and inhibition of MARCO reduced the expression of inflammatory cytokines and altered the polarization state of macrophages. This suggests that MARCO could be a potential target for the treatment of AIH.
Autoimmune hepatitis (AIH) is a progressive and chronic inflammatory disease in the liver. MARCO is a surface receptor of macrophage involving in tissue inflammation and immune disorders. Moreover, polyguanine (PolyG) is considered to bind to macrophage receptor with collagenous structure (MARCO). However, the role of MARCO and PolyG in the development and treatment of AIH still remains unclear. Therefore, this study explores the expression of MARCO and therapeutic activity of PolyG in both S100-induced AIH in mouse and Lipopolysaccharide (LPS)-treated macrophage (RAW264.7 cells). Moreover, there were significant increases in inflammatory factors and MARCO, as well as decrease in I-kappa-B-alpha (Ik-B) in the liver of AIH mice and LPS-induced cells. However, PolyG treatment significantly reversed the elevation of inflammatory cytokins, MARCO and reduction of Ik-B. In addition, PolyG treatment could downregulate the expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-beta (TRIF), decrease macrophage M1 polarization and increase macrophage M2 polarization. When hepatocytes were co-cultured with different treatment of macrophages, similar expression profile of inflammatory cytokines was observed in hepatocytes. The research revealed that MARCO expression was elevated in AIH mice. PolyG treatment and inhibition of MARCO significantly reduced inflammatory cytokines expression in the liver as well as hepatocytes and macrophages. Therefore, MARCO could be a target for the treatment of AIH.
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