Department of Infectious Diseases, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Infectious Diseases and Liver Diseases, Ningbo Medical Centre Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo, China.
J Cell Mol Med. 2022 Nov;26(22):5690-5701. doi: 10.1111/jcmm.17599. Epub 2022 Oct 25.
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.
自身免疫性肝炎（AIH）是一种肝脏进行性和慢性炎症性疾病。MARCO 是一种参与组织炎症和免疫紊乱的巨噬细胞表面受体。此外，聚鸟嘌呤（PolyG）被认为与具有胶原结构的巨噬细胞受体（MARCO）结合。然而，MARCO 和 PolyG 在 AIH 的发展和治疗中的作用仍不清楚。因此，本研究探讨了 MARCO 的表达以及 PolyG 在 S100 诱导的小鼠 AIH 和脂多糖（LPS）处理的巨噬细胞（RAW264.7 细胞）中的治疗活性。此外，AIH 小鼠和 LPS 诱导的细胞肝脏中炎症因子和 MARCO 显著增加，I-kappa-B-alpha（Ik-B）减少。然而，PolyG 治疗显著逆转了炎症细胞因子、MARCO 的升高和 Ik-B 的减少。此外，PolyG 治疗可下调 Toll 样受体 4（TLR4）和 TIR 结构域包含衔接子诱导干扰素-β（TRIF）的表达，减少巨噬细胞 M1 极化并增加巨噬细胞 M2 极化。当肝细胞与不同处理的巨噬细胞共培养时，在肝细胞中观察到相似的炎症细胞因子表达谱。研究表明，MARCO 在 AIH 小鼠中表达上调。PolyG 治疗和 MARCO 抑制可显著减少肝脏以及肝细胞和巨噬细胞中炎症细胞因子的表达。因此，MARCO 可能是治疗 AIH 的靶点。
