Abstract
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.
MeSH terms
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Animals
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Antirheumatic Agents / pharmacology
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Antirheumatic Agents / therapeutic use
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Arthritis, Rheumatoid / drug therapy
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Arthritis, Rheumatoid / enzymology*
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Arthritis, Rheumatoid / physiopathology
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Autoimmune Diseases / drug therapy
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Autoimmune Diseases / enzymology*
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Autoimmune Diseases / physiopathology
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Enzyme Activation / drug effects
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Extracellular Signal-Regulated MAP Kinases / physiology
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Fibroblasts / enzymology
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Humans
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JNK Mitogen-Activated Protein Kinases / physiology
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MAP Kinase Signaling System*
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Macrophages / enzymology
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Mice
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Mice, Transgenic
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Phosphorylation / drug effects
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Protein Processing, Post-Translational / drug effects
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Synovial Membrane / enzymology
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Synovial Membrane / pathology
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / physiology
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p38 Mitogen-Activated Protein Kinases / physiology
Substances
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Antirheumatic Agents
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Tumor Necrosis Factor-alpha
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases