Inflammatory factors stimulate expression of group II phospholipase A2 in rat cultured astrocytes. Two distinct pathways of the gene expression.
Inflammatory factors such as tumor necrosis factor (TNF), interleukin 1 (IL-1), and lipopolysaccharide (LPS) greatly enhance the expression of group II phospholipase A2 (PLA2-II) mRNA, leading to increased secretion of PLA2-II enzyme from rat-cultured astrocytes. The potent antiinflammatory agent dexamethasone suppressed the PLA2-II expression induced by LPS. In vivo studies also demonstrated that the level of PLA2-II mRNA in the brain increased with intravenous injection of LPS. These results suggest that PLA2-II in the brain plays important roles in the inflammatory response. Agents which increase intracellular cAMP concentration did not stimulate PLA2-II expression by themselves but selectively enhanced TNF-induced PLA2-II expression about 5-fold. Phorbol ester, a well known protein kinase C activator, increased the PLA2-II expression. H-7, a protein kinase C inhibitor, inhibited the LPS-induced PLA2-II expression, but did not inhibit the TNF-induced one. Therefore, we conclude that the TNF-activated pathway differs from the LPS-activated one: the former is enhanced by cAMP and the latter involves protein kinase C.
Oka
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Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Arita
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H
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010741:Phospholipases A / Q000235:genetics* / Q000378:metabolism; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2