Abstract
The role of members of the mitogen-activated protein kinase (MAPK) family on tumor necrosis factor alpha (TNF-alpha)-mediated down-regulation of col1a1 gene was studied. TNF-alpha increased extracellular-regulated kinase and Jun-N-terminal kinase phosphorylation, but these effects were not related to its inhibitory effect on alpha1(I) procollagen (col1a1) mRNA levels. Phosphorylation of p38 MAPK was decreased in response to TNF-alpha, and the specific p38 MAPK inhibitor SB203580 mimicked the effect of TNF-alpha on col1a1 mRNA levels. Transforming growth factor beta (TGF-beta) increased p38 MAPK phosphorylation and SB203580 prevented the induction of col1a1 mRNA levels by TGF-beta. These results suggest that p38 MAPK plays an important role in regulating the expression of col1a1 in hepatic stellate cells in response to cytokines.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects
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Base Sequence
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Cell Line
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Collagen Type I / genetics*
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Down-Regulation / drug effects
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Enzyme Inhibitors / pharmacology
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Hepatocytes / cytology
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Hepatocytes / drug effects*
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Hepatocytes / metabolism*
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Imidazoles / pharmacology
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation
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Pyridines / pharmacology
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RNA, Messenger / genetics*
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RNA, Messenger / metabolism*
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Rats
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Sphingomyelin Phosphodiesterase / metabolism
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Transforming Growth Factor beta / pharmacology*
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Tumor Necrosis Factor-alpha / pharmacology*
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Up-Regulation / drug effects
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p38 Mitogen-Activated Protein Kinases
Substances
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Collagen Type I
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Enzyme Inhibitors
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Imidazoles
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Pyridines
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RNA, Messenger
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Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Sphingomyelin Phosphodiesterase
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SB 203580