Open AccessPolyguanine alleviated autoimmune hepatitis through regulation of macrophage receptor with collagenous structure and TLR4‐TRIF‐NF‐κB signalling
Author(s) -
Cai Tingchen,
Xu Lanman,
Xia Dingchao,
Zhu Lujian,
Lin Yanhan,
Yu Sijie,
Zhu Kailu,
Wang Xiaodong,
Pan Chenwei,
Chen Yongping,
Chen Dazhi
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17599
Subject(s) - trif , tlr4 , macrophage polarization , inflammation , macrophage , immunology , receptor , autoimmune hepatitis , toll like receptor , immune system , medicine , biology , microbiology and biotechnology , innate immune system , hepatitis , biochemistry , in vitro
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‐β (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.