Concordant induction of prostaglandin E(2) synthase with cyclooxygenase-2 leads to preferred production of prostaglandin E(2) over thromboxane and prostaglandin D-2 in lipopolysaccharide-stimulated rat peritoneal macrophages

Rat peritoneal macrophages were stimulated with lipopolysaccaride (LPS) for various periods and their ability to convert exogenous arachidonic acid to various prostanoids was examined. Unstimulated cells, which expressed cyclooxygenase (COX)-1 but not COX-2, produced thromboxane (TX) B-2 > prostaglandin (PG) D-2 > PGE(2), whereas cells stimulated for 6-12 h with LPS exhibited marked increase in conver sion to PGE(2), which paralleled COX-2 induction, with minimal change in conversion to TXB(2) and PGD(2). Pharmacological studies showed that formation of PGE(2) was mediated predominantly by COX-2, PGD(2) by COX-1, and TXB(2) by both COX-1 and COX-2 depending upon the timing of LPS stimulation. Measurement of the conversion of exogenous PGH(2) to each prostanoid in cell lysates demonstrated LPS-dependent increase in PGE(2) synthase activity that was degenerated by pretreatment with actinomycin D or cycloheximide. Thus, concordant induction of terminal PGE(2) synthase with COX-2 leads to the preferred production of PGE(2) to TXB(2) and PGD(2) by LPS-stimulated macrophages. (C) 1997 Academic Press