Glucocorticoids suppress group II phospholipase A2 production by blocking mRNA synthesis and post-transcriptional expression.
We investigated the effects of glucocorticoids on group II phospholipase A2 (PLA2) expression in rat cultured smooth muscle cells. Both forskolin-induced and tumor necrosis factor (TNF)-induced PLA2 release responses were almost completely blocked by 10 and 100 nM dexamethasone, respectively, as assayed by protein blotting and PLA2 activity assays. Dexamethasone-mediated inhibition of PLA2 release appeared to be mediated by the glucocorticoid receptor. Dexamethasone at concentrations greater than 10 nM inhibited forskolin-induced elevation of the group II PLA2 mRNA level but not TNF-induced elevation. These data suggest that the mechanism mediating forskolin-induced mRNA accumulation is sensitive to glucocorticoids, but the mechanism mediating the TNF-induced accumulation is not. Inhibition of TNF-induced PLA2 release by glucocorticoids may be explained by the blocking of post-transcriptional synthesis of the group II PLA2.
Nakano
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Ohara
O
O
Teraoka
H
H
Arita
H
H
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010740:Phospholipases / Q000235:genetics*; D010741:Phospholipases A / Q000096:biosynthesis / Q000235:genetics*; D054467:Phospholipases A2; D011374:Progesterone / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D005938:Glucocorticoids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D011374:Progesterone; D003907:Dexamethasone; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2