Interleukin-1 alpha induces the accumulation of cytosolic phospholipase A2 and the release of prostaglandin E2 in human fibroblasts.
Treatment of the human lung fibroblast cell line, WI-38, with interleukin-1 alpha (IL-1 alpha) results in a large increase in the production of cytosolic phospholipase A2 (cPLA2) and prostaglandin E2 (PGE2). The IL-1-induced accumulation of cPLA2 is closely correlated with increased PGE2 release. In contrast to cPLA2, the level of cyclooxygenase remains unchanged following IL-1 alpha treatment. The glucocorticoid, dexamethasone, blocks the IL-1 alpha-mediated increases in both cPLA2 and PGE2 without affecting the cyclooxygenase level. Taken together, these data suggest that in these cells, the regulation of prostaglandin production by IL-1 and glucocorticoid can be attributed to the level of cPLA2. These results provide a new mechanism for the effect of IL-1 and glucocorticoids on eicosanoid synthesis and provide additional support for an important role of cPLA2 in the inflammatory response.
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Genetics Institute, Inc., Cambridge, Massachusetts 02140.
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DeWitt
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D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins; D000001:Calcimycin; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone