Ralph Jennifer A, Morand Eric F
Monash University, Department of Medicine, Centre for Inflammatory Diseases, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne 3168, Australia.
Expert Opin Ther Targets. 2008 Jul;12(7):795-808. doi: 10.1517/14728222.12.7.795.
Rheumatoid arthritis (RA) represents a challenge for therapeutic interventions due to complex inflammatory signalling pathways underlying its pathogenesis. The MAPK signalling network, a major effector limb of the inflammatory lesion, is an attractive therapeutic target. MAPK phosphatases (MKPs), endogenous negative regulators of MAPK signalling, have received increasing recognition as modulators of inflammatory and immune responses, and hence as a potential therapeutic avenue for RA.
To present the rationale for therapeutically targeting MAPK signalling and explore the case for addressing MKP1 as a novel therapeutic strategy for RA.
We summarise literature describing the importance of MAPK signalling in RA and review reports describing the roles of MKPs in modulating innate and adaptive immune responses. Finally we expand on the role of MKP1 in RA pathogenesis and explore data defining MKP1 as a mediator of glucocorticoid action.
MKP1 constitutes an exciting, novel potential therapeutic target for RA.
类风湿关节炎（RA）因其发病机制中复杂的炎症信号通路而对治疗干预构成挑战。丝裂原活化蛋白激酶（MAPK）信号网络是炎症病变的主要效应分支，是一个有吸引力的治疗靶点。MAPK磷酸酶（MKPs）是MAPK信号的内源性负调节因子，作为炎症和免疫反应的调节剂，因而作为RA的一种潜在治疗途径受到越来越多的认可。
阐述靶向MAPK信号进行治疗的基本原理，并探讨将MKP1作为RA的一种新型治疗策略的情况。
我们总结了描述MAPK信号在RA中的重要性的文献，并回顾了描述MKPs在调节先天性和适应性免疫反应中的作用的报告。最后，我们详述了MKP1在RA发病机制中的作用，并探讨了将MKP1定义为糖皮质激素作用介质的数据。
MKP1是RA一个令人兴奋的新型潜在治疗靶点。
