The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis.
Chronic inflammatory processes are based on a sustained and tightly 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. The mirrors of this outside communication world are intracellular transcription factor pathways, which shuttle 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 (p38MAPK). The signalling 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 summarises the current knowledge of activation, regulation and function of the p38MAPK pathway but also examines the role of this pathway in clinical disease. It gives an overview of current evidence of p38MAPK activation in inflammatory arthritis and elaborates the key molecular determinants which contribute to p38MAPK activation in joint disease.
Schett
G
G
Department of Internal Medicine III, University of Erlangen, D-91054 Erlangen, Germany. Georg.Schett@uk-erlangen.de
Zwerina
J
J
Firestein
G
G
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000503:physiopathology*; D001862:Bone Resorption / Q000201:enzymology; D002358:Cartilage, Articular / Q000201:enzymology; D004730:Endothelium, Vascular / Q000503:physiopathology; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D013585:Synovitis / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*