受体相互作用蛋白家族在炎症中的作用研究进展

Research progress on receptor interacting proteins in inflammation

受体相互作用蛋白(RIP)家族是一组苏氨酸/丝氨酸蛋白激酶,具有相对保守的激酶结构域和不同的非激酶结构域,参与固有免疫应答、炎症等生理和病理过程。近年来研究表明,RIP家族通过参与坏死复合物的形成介导细胞坏死、触发炎症反应,其中RIP1和RIP3与细胞坏死的关系尤为密切。细胞坏死是一种精密调控的细胞死亡方式。通过TNF信号通路和Toll样受体信号通路传递的死亡信号可招募并磷酸化混合谱系激酶结构域蛋白,最终导致细胞崩解死亡,而细胞崩解后释放的胞内物质可触发炎症反应。本文着重阐述RIP家族介导细胞坏死和炎症发生所涉及的主要信号通路及分子机制,简述了RIP家族在相关炎症性疾病中的重要作用,并对RIP作为炎症性疾病治疗靶点的可能性进行了展望。

Receptor interacting proteins（ RIPs） are a group of threonine/serine protein kinases,which have relatively conserved kinase domains and different nonkinase domains,and are involved in physiological and pathological processes including innate immune response and inflammation. In recent years,many studies have shown that RIPs mediate cell necroptosis and triggers inflammatory responses by participating in the formation of necrotic complexes,and RIP1 and RIP3 are particularly closely related to cell necrosis. Cell necroptosis is a well-regulated way of cell death. The death signal that transmit through the TNF signaling pathway and the Toll-like receptor signaling pathway can recruit and phosphorylate mixed lineage kinase domain-like protein（ MLKL）,and eventually leading to disintegration and death of cells,and the release of cells intercellular material after cell disintegration can trigger an inflammatory reaction. This review mainly focuses on the major signaling pathways and molecular mechanisms that are involved in the mediation of necrosis and inflammation by RIPs. It also highlights the importance of RIPs in the development of inflammatory diseases and their potentials as therapeutic targets for inflammatory diseases.