Abstract
We examined the role of p38 mitogen-activated protein (MAP) kinase in the tumor necrosis factor alpha (TNF-alpha)- or interleukin-1beta (IL-1beta)-induced production of interleukin-6 (IL-6) and interleukin-8 (IL-8) in fresh rheumatoid synovial fibroblast (RSF) cultures concomitantly with the induction of p38 MAP kinase activity. Pretreatment of RSF with a specific p38 MAP kinase inhibitor, SB203580, blocked the induction of IL-6 and IL-8 without affecting nuclear translocation of nuclear factor kappaB (NF-kappaB) or IL-6 and IL-8 mRNA levels. These findings suggest that p38 MAP kinase inhibitor may have synergistic, rather than additive, effect for the treatment of rheumatoid arthritis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arthritis, Rheumatoid / drug therapy
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Arthritis, Rheumatoid / metabolism
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Cell Nucleus / metabolism
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Cells, Cultured
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Humans
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Imidazoles / pharmacology*
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Interleukin-1
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Interleukin-6 / biosynthesis*
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Interleukin-6 / genetics
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Interleukin-8 / biosynthesis*
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Interleukin-8 / genetics
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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NF-kappa B / metabolism
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Pyridines / pharmacology*
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RNA, Messenger / biosynthesis
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Synovial Membrane / metabolism*
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Tumor Necrosis Factor-alpha
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p38 Mitogen-Activated Protein Kinases
Substances
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Enzyme Inhibitors
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Imidazoles
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Interleukin-1
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Interleukin-6
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Interleukin-8
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NF-kappa B
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Pyridines
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580