17-β estradiol enhances prostaglandin E2 production in human U937-derived macrophages

Prostaglandins (PGs) are potent eicosanoid lipid mediators that have been implicated in numerous homeostatic functions and inflammation. Estrogens have been shown to regulate the expression of genes in lipid metabolism in many cellular systems. In this study, the activation of macrophages and the modulation of PG release by estrogens were examined. The effects of 17-alpha and 17-beta estradiols, phytoestrogen Genistein and several selective estrogen receptor modulators on the release of PGE(2) were investigated in human U937-derived macrophages. 17-beta estradiol caused an enhancement of PGE(2) production in a time- and dose-dependent manner. Treatment of macrophages with 17-beta estradiol elicited an increased arachidonic acid (AA) release and an up-regulation of both cyclooxygenesis-1 and cyclooxygenasis-2 enzymes at both the transcript and protein levels. In addition, immunostaining of nuclear estrogen receptor alpha and the observation of ICI182 780 blockade of PGE2 production indicated that 17-beta estradiol-induced PGE(2) release was mainly through nuclear estrogen receptor alpha.