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 ob served 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-regulat ion of LPL expression. Using indomethacin (INDO), an inhibitor of cycl o-oxygenase and prostaglandins production, we determined that PGE(2) a cts as a feedback inhibitor of LPL expression. We found that inhibited secretion of LPL protein in lipopolysaccharide (LPS)-treated macropha ges 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 actio n may play an important physiological role in the regulation of LPL ge ne expression during bacterial infections.