Lab of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2022 May 30;13:896473. doi: 10.3389/fimmu.2022.896473. eCollection 2022.
Inflammasomes are multiprotein complexes that can sense danger signals and activate caspase-1 to mediate pro-inflammatory cytokines release and pyroptotic cell death. There are two main canonical and non-canonical signaling pathways that trigger inflammasome activation. Inflammasomes are expressed and assembled in parenchymal and nonparenchymal cells in response to liver injury in the liver. Additionally, the hepatocytes, biliary epithelial cells (cholangiocytes), hepatic stellate cells (HSCs), hepatic macrophages, and liver sinusoidal endothelial cells (LSECs) contribute to liver fibrosis different mechanisms. However, the underlying mechanism of the inflammasome and pyroptosis in these liver cells in liver fibrosis remains elusive. This review summarizes the activation and function of inflammasome complexes and then discusses the association between inflammasomes, pyroptosis, and liver fibrosis. Unlike other similar reviewers, we will focus on the effect of inflammasome activation and pyroptosis in the various liver cells during the development of liver fibrosis. We will also highlight the latest progress of pharmacological intervention in inflammasome-mediated liver fibrosis.
炎症小体是一种多蛋白复合物，可以感知危险信号，并激活半胱氨酸天冬氨酸蛋白酶-1（caspase-1），从而介导促炎细胞因子的释放和细胞焦亡。有两种主要的经典和非经典信号通路可以触发炎症小体的激活。炎症小体在肝脏损伤时，在实质细胞和非实质细胞中表达和组装。此外，肝细胞、胆管上皮细胞（胆管细胞）、肝星状细胞（HSCs）、肝巨噬细胞和肝窦内皮细胞（LSECs）通过不同的机制参与肝纤维化。然而，炎症小体和细胞焦亡在肝纤维化这些肝细胞中的潜在机制仍不清楚。这篇综述总结了炎症小体复合物的激活和功能，然后讨论了炎症小体、细胞焦亡与肝纤维化之间的关系。与其他类似的综述不同，我们将重点关注炎症小体激活和细胞焦亡在肝纤维化发展过程中各种肝细胞中的作用。我们还将重点介绍炎症小体介导的肝纤维化的药理学干预的最新进展。
