Concordant induction of prostaglandin E2 synthase with cyclooxygenase-2 leads to preferred production of prostaglandin E2 over thromboxane and prostaglandin D2 in lipopolysaccharide-stimulated rat peritoneal macrophages.
Journal: 1997/February - Biochemical and Biophysical Research Communications
ISSN: 0006-291X
Abstract:
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) B2>> prostaglandin (PG) D2>> PGE2, whereas cells stimulated for 6-12 h with LPS exhibited marked increase in conversion to PGE2, which paralleled COX-2 induction, with minimal change in conversion to TXB2 and PGD2. Pharmacological studies showed that formation of PGE2 was mediated predominantly by COX-2, PGD2 by COX-1, and TXB2 by both COX-1 and COX-2 depending upon the timing of LPS stimulation. Measurement of the conversion of exogenous PGH2 to each prostanoid in cell lysates demonstrated LPS-dependent increase in PGE2 synthase activity that was degenerated by pretreatment with actinomycin D or cycloheximide. Thus, concordant induction of terminal PGE2 synthase with COX-2 leads to the preferred production of PGE2 to TXB2 and PGD2 by LPS-stimulated macrophages.
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