Abstract
The mechanism by which p38 mitogen-activated protein kinase (MAPK) regulates the induction of cyclooxygenase (COX)-2 by interleukin-1 (IL-1) has been investigated in HeLa cells. SB 203580, an inhibitor of p38 MAPK, in the range 0.1-1 microM inhibited IL-1-stimulated PGE2 (but not arachidonic acid) release and this was associated with inhibition of induction of COX-2 protein and mRNA. IL-1 stimulated COX-2 transcription in HeLa cells about 2-fold as judged by both reporter gene and nuclear run-on assays. The inhibitor had no significant effect on this. However, in cells previously stimulated with IL-1 it caused rapid destabilisation of COX-2 mRNA independently of on-going transcription. The results suggest a novel function for p38 MAPK in the regulation of mRNA stability.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arachidonic Acids / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cyclooxygenase 2
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Dinoprostone / antagonists & inhibitors
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Enzyme Induction
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Enzyme Inhibitors / pharmacology*
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HeLa Cells
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Humans
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Imidazoles / pharmacology*
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Interleukin-1 / pharmacology
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Isoenzymes / metabolism*
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JNK Mitogen-Activated Protein Kinases
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Membrane Proteins
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Mitogen-Activated Protein Kinases*
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Pyridines / pharmacology*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism*
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p38 Mitogen-Activated Protein Kinases
Substances
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Arachidonic Acids
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Enzyme Inhibitors
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Imidazoles
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Interleukin-1
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Isoenzymes
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Membrane Proteins
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Pyridines
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RNA, Messenger
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Calcium-Calmodulin-Dependent Protein Kinases
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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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Dinoprostone
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SB 203580