title: Type 1 IFN inhibits the growth factor deprived apoptosis of cultured human aortic endothelial cells and protects the cells from chemically induced oxidative cytotoxicity.
abstract: It has been shown that the genesis of atherosclerotic lesions is resulted from the injury of vascular endothelial cells and the cell damage is triggered by oxygen radicals generated from various tissues. Human vascular endothelial cells can survive and proliferate depending on growth factors such as VEGF or basic FGF and are induced apoptosis by the deprivation of growth factor or serum. It was found that type 1 IFN inhibits the growth factor deprived cell death of human aortic endothelial cells (HAEC) and protects the cells from chemically induced oxidative cytotoxicity. The anti-apoptotic effects of type 1 IFN were certified by flow cytometry using annexin-V-FITC/PI double staining and cell cycle analysis, fluorescence microscopy using Hoechst33342 and PI, colorimetric assay for caspase-3 activity, p53 and bax mRNA expressions, and cell counts. It was considered that IFN-β inhibits the executive late stage apoptosis from the results of annexin-V-FITC/PI double staining and the inhibition of caspase-3 activity, and that the anti-apoptotic effect might be owing to the direct inhibition of the apoptotic pathway mediated by p53 from the transient down-regulation of bax mRNA expression. Whereas, type 1 IFN protected the cells from the oxidative cytotoxicity induced by tertiary butylhydroperoxide (TBH) under the presence of Ca(2+). The effects of IFN-β is more potent inhibitor of cell death than IFN-α. These results indicate that type 1 IFN, especially IFN-β may be useful for the diseases with vascular endothelium damage such as atherosclerosis or restenosis after angioplasty as a medical treatment or a prophylactic.
authors: Department of Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Shirokanedai, Tokyo, 108-8639, Japan. sano_e@mgs.k.u-tokyo.ac.jp
authors: Emiko
authors: E
authors: Sano
authors: Shinnya
authors: S
authors: Tashiro
authors: Hisashi
authors: H
authors: Tadakuma
authors: Toshiaki
authors: T
authors: Takei
authors: Takuya
authors: T
authors: Ueda
authors: Kouhei
authors: K
authors: Tsumoto
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D001011:Aorta / Q000166:cytology; D017209:Apoptosis; D001562:Benzimidazoles; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D019610:Cytoprotection; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D013194:Staining and Labeling; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D017304:Annexin A5; C494826:BAX protein, human; D001562:Benzimidazoles; D016898:Interferon-alpha; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D016899:Interferon-beta; D020122:tert-Butylhydroperoxide; C505407:CASP3 protein, human; D053148:Caspase 3; D016650:Fluorescein-5-isothiocyanate; C017807:bisbenzimide ethoxide trihydrochloride; D002118:Calcium