title: Investigations into the mechanism of toxicity of lipopolysaccharide (LPS) in bovine aortic endothelial cells.
abstract: The cytotoxic effect of lipopolysaccharide (LPS) was examined on bovine aortic endothelial cell proliferation in vitro. These LPS-induced cytotoxicity (IC50 = 20 ng/ml) was not inhibitable by substances regulating the formation of nitric oxide (NO). e.g. by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, and by the glucocorticoid dexamethasone, an inhibitor of the induction of NO synthase. Also other substances which inhibit the generation or action of oxygen radicals, as glutathion and the xanthine oxidase inhibitor allopurinol did not prevent the cytotoxic effect of LPS. Only tyrphostin B46, an inhibitor of tyrosine kinase, attenuated the toxic LPS effect, suggesting that the LPS-induced cytotoxicity in bovine aortic endothelial cell cultures is mediated by a specific tyrosine kinase, and not by NO or oxygen radicals.
authors.affiliation: Research Institute for Molecular Pharmacology, Department of Cellular and Biochemical Pharmacology, Berlin.
authors.forename: M F
authors.initials: MF
authors.lastname: Melzig
authors.forename: R
authors.initials: R
authors.lastname: Loose
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000633:toxicity*; D009569:Nitric Oxide / Q000096:biosynthesis; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020032:Tyrphostins
chemical_list: D001597:Benzylidene Compounds; D008070:Lipopolysaccharides; D009570:Nitriles; D020032:Tyrphostins; C095713:alpha-cyano-(3,4-dihydroxy)-N-(3-phenylpropyl)cinnamide; D009569:Nitric Oxide; D000001:Calcimycin; D003907:Dexamethasone; D011505:Protein-Tyrosine Kinases