title: TNF-alpha-induced inhibition of PC synthesis by human type II pneumocytes is sequentially mediated by PGE2 and NO.
abstract: Tumor necrosis factor-alpha (TNF-alpha)-induced inhibition of surfactant synthesis participates in the pathogenesis of the acute respiratory distress syndrome. We examined the ability of human type II pneumocytes to produce nitric oxide (NO) in the presence of TNF-alpha as well as the role of NO and prostaglandin (PG) E2 in the transduction of the cytokine signal. Multiple organ donors were used as a source of lung tissue. After 24-h preculture, type II pneumocytes were cultured for 18 h in the presence or absence of additives. The D-[U-14C] glucose incorporation into phosphatidylcholine (PC) was selectively inhibited by TNF-alpha, PGE2, sodium nitroprusside (SNP), or 8-bromoguanosine 3',5'-cyclic monophosphate. The effect of TNF-alpha was attenuated by indomethacin, N omega-nitro-L-arginine methyl ester (NAME), or methylene blue (MB). The effect of PGE2 was attenuated by NAME, while that of SNP was reversed by MB but not by indomethacin. TNF-alpha induced an increase in PGE2 and guanosine 3',5'-cyclic monophosphate cell content and in the NO release to the medium. NAME did not affect PGE2 production, while indomethacin blunted NO generation. Our results suggest that NO generation, secondary to PGE2 production, is responsible for the TNF-alpha-induced inhibition of PC synthesis by human type II pneumocytes.
authors.affiliation: Department of Biochemistry (Facultad de Medicina), Universidad Complutense, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Vara
authors.forename: J
authors.initials: J
authors.lastname: Arias-Díaz
authors.forename: C
authors.initials: C
authors.lastname: García
authors.forename: J
authors.initials: J
authors.lastname: Hernández
authors.forename: J L
authors.initials: JL
authors.lastname: Balibrea
mesh_terms: D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D010713:Phosphatidylcholines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015232:Dinoprostone