Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.
Scientifc Research Center, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.
Gene. 2024 Nov 30;928:148768. doi: 10.1016/j.gene.2024.148768. Epub 2024 Jul 14.
Although antiviral drugs can effectively inhibit hepatitis B virus (HBV) replication, the maintenance of chronic inflammation in the liver is still considered to be an important cause for the progression of HBV-related liver disease to liver fibrosis and advanced liver disease. As an endogenous inhibitory receptor of IL-1R and TLR signaling pathways, single immunoglobulin interleukin-1-related receptor (SIGIRR) has been proven to reduce inflammation in tissues to maintain system homeostasis. However, the relationship between SIGIRR expression and HBV replication and inflammatory pathway activation in hepatocytes remains unclear. In this study, hepatitis B virus X protein (HBx) upregulated MyD88 in liver cells, promoting NF-κB signaling and inflammatory factor production with LPS treatment, and the cell supernatant accelerated the activation and collagen secretion of hepatic stellate cells. However, SIGIRR overexpression suppressed HBx-mediated MyD88/NF-κB inflammatory signaling activation and inflammatory cytokine production induced by LPS in hepatocytes and HBV replication hepatocytes. Although we did not find any effect of SIGIRR on HBV replication in vitro, this study investigated the role of SIGIRR in blocking the proinflammatory function of HBx, which may provide a new idea for the treatment of chronic hepatitis B.
虽然抗病毒药物可以有效抑制乙型肝炎病毒 (HBV) 的复制，但肝脏内慢性炎症的持续存在仍被认为是 HBV 相关肝病进展为肝纤维化和晚期肝病的重要原因。作为 IL-1R 和 TLR 信号通路的内源性抑制受体，单免疫球蛋白白细胞介素-1 相关受体 (SIGIRR) 已被证明可减轻组织炎症，维持系统内环境平衡。然而，SIGIRR 表达与 HBV 在肝细胞中的复制和炎症途径激活之间的关系尚不清楚。在本研究中，乙型肝炎病毒 X 蛋白 (HBx) 在肝细胞中上调了 MyD88，促进了 NF-κB 信号转导和 LPS 处理时炎症因子的产生，细胞上清液加速了肝星状细胞的激活和胶原分泌。然而，SIGIRR 的过表达抑制了 HBx 介导的 LPS 诱导的肝细胞中 MyD88/NF-κB 炎症信号转导激活和炎症细胞因子的产生以及 HBV 复制。尽管我们没有发现 SIGIRR 在体外对 HBV 复制有任何影响，但本研究探讨了 SIGIRR 阻断 HBx 促炎功能的作用，这可能为慢性乙型肝炎的治疗提供新的思路。
