title: Cytotoxicity of IFN-gamma and TNF-alpha for vascular endothelial cell is mediated by nitric oxide.
abstract: Endothelial cell injury is a critical event in tissue damage accompanying inflammation, in which both inflammatory cytokines and reactive oxygen species may play pivotal roles, although the exact mechanism has not yet been clarified. We found that combined stimulation with interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) induced both cytotoxicity to murine vascular endothelial cell line F-2 and an increase in nitric oxide (NO). Therefore, in the present study, the implication of NO in cytotoxicity was examined. A potent iNOS-specific inhibitor ONO-1714 completely blocked both cytokine-induced cytotoxicity and NO production. NO scavengers such as carboxy-PTIO and hemoglobin blocked cytotoxicity. Moreover, exogenous NO from NOC 18 also caused cytotoxicity. These results together demonstrated that cytotoxicity of IFN-gamma and TNF-alpha for endothelial cell F-2 was mediated by NO, suggesting a pathogenic role of cytokine-induced NO production in endothelial damage under inflammatory conditions.
authors.affiliation: Department of Dermatology, Kyoto University, Graduate School of Medicine, Kyoto 606-8507, Japan. ymokj33@kuhp.kyoto-u.ac.jp
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamaoka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Michiko
authors.initials: M
authors.lastname: Kawanishi
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Toda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000633:toxicity*; D007700:Kinetics; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
chemical_list: C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma