title: Prostaglandin E2 attenuates hyperoxia-induced injury in cultured rabbit tracheal epithelial cells.
abstract: We assessed the kinetics of hyperoxia-induced prostaglandin E2 (PGE2) production by cultured rabbit tracheal epithelial (TE) cells with different inherent capacities to generate PGE2 and the role of endogenous PGE2 production in protecting these cells from hyperoxic injury. Rabbit TE cells grown to confluence with or without lipid supplements [0.1% Excyte III (Miles-Pentex) and 1 microM arachidonic acid] were exposed for 2 h to control (5% CO2/air) or hyperoxic (5% CO2/90% O2) atmospheres at a gas-fluid interface. Serial cell culture effluents collected during exposure were analyzed for PGE2 by enzyme-linked immunoassay. Basal PGE2 production by lipid-supplemented cells was approximately 3-fold greater than that by unsupplemented cultures (p less than 0.01). In lipid-supplemented cells, PGE2 production doubled after 15 min of hyperoxic exposure (p less than 0.05) and then declined to approximately 50% of initial levels, whereas exposure to 5% CO2/air did not significantly change PGE2 production. In unsupplemented cells, neither control nor hyperoxic exposure altered PGE2 production. Hyperoxia-exposed TE cells had decreased ability to convert 10 microM exogenous arachidonic acid to PGE2, suggesting hyperoxia-induced inhibition of the enzymes involved in PGE2 synthesis. Lipid-supplemented cells were less susceptible to hyperoxic injury than unsupplemented monolayers, as evidenced by increased viability (trypan blue exclusion) and decreased generation of lipid peroxides (thiobarbituric acid reactive substances). Addition of exogenous PGE2 to unsupplemented cultures at concentrations that were produced by lipid-supplemented cells (2 ng/mL every 15 min) during hyperoxic exposure eliminated these differences in hyperoxia-induced lipid peroxidation and cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: P A
authors.initials: PA
authors.lastname: Dennery
authors.forename: R W
authors.initials: RW
authors.lastname: Walenga
authors.forename: C M
authors.initials: CM
authors.lastname: Kramer
authors.forename: S E
authors.initials: SE
authors.lastname: Alpert
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism; D010100:Oxygen; D011817:Rabbits; D014132:Trachea / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism
chemical_list: D008054:Lipid Peroxides; D016718:Arachidonic Acid; D015232:Dinoprostone; D010100:Oxygen