p38 MAPK通路的活性调控及其在类风湿性关节炎中的作用

The p38 Mitogen-Activated Protein Kinase Pathway in Rheumatoid Arthritis

类风湿性关节炎过程涉及多细胞间的信号网络持续的调控。该网络包括胞外介质如细胞因子、趋化因子和基质金属蛋白酶,其协调各细胞参与慢性炎症过程。相对应的是胞内转录因子通路,其主要将炎症刺激信息传递给细胞核。丝裂原活化蛋白激酶(MAPKs)信号通路中p38 MAPK信号通路对慢性炎症的诱导及维持起至关重要的作用,因此针对该通路上的分子靶点研制出相应的小分子抑制剂用于控制炎症发展。本文通过总结p38 MAPK通路的多种功能作用和活性调节,对其在类风湿性关节炎中的作用做简要综述。

Rheumatoid arthritis processes are based on a sustained regulated communication network among different cells types. This network comprises extracellular mediators such as cytokines, chemokines and matrix degrading proteases, which orchestrate the participation of cells in the chronic inflammatory process. Intracellular transcription factor pathways are corresponding with this outside communication world, which transfer information about inflammatory stimuli to the cell nucleus. This review examines the function of one key signal transduction pathway of inflammation—the p38 mitogen-activated protein kinases (p38 MAPK). The p38 MAPK signalling pathway is considered crucial for the induction and maintenance of chronic inflammation, and thus its components emerge as interesting molecular targets of small molecule inhibitors for controlling inflammation. This review not only summarizes the current knowledge of activation, regulation and function of the p38 MAPK pathway but also examines the role of this pathway in rheumatoid arthritis.