Lipopolysaccharide-induced expression of prostaglandin H synthase-2 in alveolar macrophages is inhibited by dexamethasone but not by aspirin.
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.
O'Sullivan
M G
MG
Department of Medicine, Wake Forest University Medical Center, Winston-Salem, NC 27157-1042.
Huggins
E M
EM
McCall
C E
CE
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
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013929:Thromboxane B2; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin