MAPK signalling in rheumatoid joint destruction: can we unravel the puzzle?
Mitogen-activated protein kinases (MAPKs) have been associated with the pathogenesis of rheumatoid arthritis (RA), but the individual contributions of the three MAPK family members are incompletely understood. Although previous data have established a role for c-Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) in different animal models of arthritis, most recent data indicate that the stable activation of p38 MAPK and in part of ERK significantly contributes to destructive arthritis in mice transgenic for human tumour necrosis factor-alpha. These data highlight the complexity of MAPK signalling in arthritis and provide a basis for the design of novel strategies to treat human RA.
Meyer
Lars-Henrik
LH
Division of Molecular Medicine of Musculoskeletal Tissue, Department of Orthopaedics, University Hospital of Munster, Munster, Germany.
Pap
Thomas
T
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013583:Synovial Membrane / Q000201:enzymology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases