Prostaglandins inhibit lipoprotein lipase gene expression in macrophages.
In the present investigation of the effects of prostaglandin E2 (PGE2) on lipoprotein lipase (LPL) gene expression in macrophages, we observed that treatment of macrophages with PGE2 increased the levels of adenosine 3',5'-cyclic monophosphate (cAMP), while the addition of exogenous 5-bromo-cAMP to macrophage cultures resulted in down-regulation of LPL expression. Using indomethacin (INDO), an inhibitor of cyclo-oxygenase and prostaglandins production, we determined that PGE2 acts as a feedback inhibitor of LPL expression. We found that inhibited secretion of LPL protein in lipopolysaccharide (LPS)-treated macrophages could be restored to control levels by the addition of INDO to the medium. In contrast, INDO did not reverse the inhibition of LPL mRNA induced by LPS. Overall, our results have demonstrated that PGE2 is a potent inhibitor of LPL gene expression and indicated that its action may play an important physiological role in the regulation of LPL gene expression during bacterial infections.
Institute of Immunology, Central University of Venezuela, Caracas.
J B
JB
Desanctis
L
L
Varesio
D
D
Radzioch
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects
D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D008071:Lipoprotein Lipase; D015232:Dinoprostone; D007213:Indomethacin