The p38 mitogen activated protein kinase (MAPK) pathway in rheumatoid arthritis

Georg Schett ^1*, Jochen Zwerina ¹ and Gary Firestein ²

¹ Department of Internal Medicine III, University of Erlangen, Germany
² Division of Rheumatology, UCSD, San Diego, CA, United States

^* To whom correspondence should be addressed. E-mail: georg.schett{at}uk-erlangen.de.

Accepted 8 August 2007

Abstract

Chronic inflammatory processes are based on a sustained and tightly regulated communication network among different cells types. This network is based on extracellular mediators such as cytokines, chemokines and matrix degrading proteases, which orchestrate the participation of cells in the chronic inflammatory process. The mirrors of this outside communication world are intracellular transcription factor pathways, which shuttle information about inflammatory stimuli to the cell nucleus. This review addresses the function of one key signal transduction pathway of inflammation- the p38 mitogen- activated protein kinases (p38MAPK). The signaling pathway is considered as crucial for the induction and maintenance of chronic inflammation and its components thus 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 p38MAPK pathway but also links to the role of this pathway in clinical disease. It gives on overview of current evidence of p38MAPK activation in inflammatory arthritis and elaborates the key molecular determinants, which contribute to p38MAPK activation in joint disease.

Keywords: bone destruction, cartilage damage, p38MAPK, rheumatoid arthritis, synovitis

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