MAPK phosphatases as novel targets for rheumatoid arthritis.
BACKGROUND
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.


OBJECTIVE
To present the rationale for therapeutically targeting MAPK signalling and explore the case for addressing MKP1 as a novel therapeutic strategy for RA.


METHODS
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.


CONCLUSIONS
MKP1 constitutes an exciting, novel potential therapeutic target for RA.
Ralph
Jennifer A
JA
Monash University, Department of Medicine, Centre for Inflammatory Diseases, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne 3168, Australia.
Morand
Eric F
EF
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D016503:Drug Delivery Systems; D054638:Dual Specificity Phosphatase 1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D054639:Mitogen-Activated Protein Kinase Phosphatases; D054638:Dual Specificity Phosphatase 1