PROSTAGLANDINS INHIBIT LIPOPROTEIN-LIPASE GENE-EXPRESSION IN MACROPHAGES

In the present investigation of the effects of prostaglandin E(2) (PGE(2)) on lipoprotein lipase (LPL) gene expression in macrophages, we observed that treatment of macrophages with PGE(2) 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 PGE(2) 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 PGE(2) 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.