title: Lipopolysaccharide-induced expression of prostaglandin H synthase-2 in alveolar macrophages is inhibited by dexamethasone but not by aspirin.
abstract: Alveolar macrophages cultured with lipopolysaccharide release markedly increased amounts of prostanoids upon subsequent stimulation, an effect that is due to induction of prostaglandin H synthase-2 (J. Biol. Chem., (1992), 267, 14545-14550, and Biochem. Biophys. Res. Comm., (1992), 187, 1123-1127). The effects of dexamethasone and aspirin on this enhanced formation of thromboxane by stimulated lipopolysaccharide-primed alveolar macrophages were investigated. Under conditions of maximum inhibition, dexamethasone and aspirin decreased the formation of thromboxane by approximately 50% and 80%, respectively. Expression of lipopolysaccharide-induced prostaglandin H synthase-2 in dexamethasone-treated macrophages was similarly inhibited by about 50%, as determined by Northern blot and immunoprecipitation. In contrast, levels of lipopolysaccharide-induced prostaglandin H synthase-2 mRNA and protein were not reduced in aspirin-treated macrophages. We conclude that inhibition of prostaglandin H synthase-2 expression represents a mechanism by which dexamethasone, but not aspirin, may inhibit prostanoid formation by alveolar macrophages.
authors: Department of Medicine, Wake Forest University Medical Center, Winston-Salem, NC 27157-1042.
authors: M G
authors: MG
authors: O'Sullivan
authors: E M
authors: EM
authors: Huggins
authors: C E
authors: CE
authors: McCall
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013929:Thromboxane B2; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin