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 arachidon ic 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 f or 6-12 h with LPS exhibited marked increase in conver sion to PGE(2), which paralleled COX-2 induction, with minimal change in conversion t o 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) synthas e 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 P GD(2) by LPS-stimulated macrophages. (C) 1997 Academic Press