title: Effect of captopril on radiation-induced TGF-β1 secretion in EA.Hy926 human umbilical vein endothelial cells.
abstract: The pathophysiological mechanism involved in the sustained endothelial secretion of cytokines that leads to fibrosis 6-16 months after radiotherapy remains unclear. Angiotensin II (Ang II) is produced by the endothelium in response to stressing stimuli, like radiation, and may induce the synthesis of TGF-β, a profibrotic cytokine. In this study we tested the hypothesis that captopril, an angiotensin-converting enzyme (ACE) inhibitor, inhibits or attenuates radiation-induced endothelial TGF-β1 secretion. The human endothelial hybrid cell line EA.HY926 was irradiated with split doses of x-rays (28 Gy delivered in 14 fractions of 2 Gy). TGF-β1 mRNA, TNF-α mRNA and TGF-β1 protein levels were evaluated by RT-PCR and western blotting each month until the fifth month post radiation. Ang II was detected using radioimmunoassays, NF-κB activity was examined using EMSA, and western blotting was used to detect the expression of Iκ-Bα. To explore the role of Ang II on radiation-induced TGF-β1 release and Iκ-Bα expression, captopril was added to cultured cells before, during, or after irradiation. Sustained strong expression of TGF-β1 was observed after conventional fractionated irradiation. TNF-α, Ang II, and NF-κB activity were also increased in EA.Hy926 cells after radiation. Captopril decreased Ang II expression, inhibited the NF-κB pathway and reduced TGF-β1 expression. These data suggest that captopril might protect the endothelium from radiation-induced injury.
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.|Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.|Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.
authors.forename: Jingni
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.|Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.|Hubei Clinical Cancer Study Centre, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.
authors.forename: Baiyu
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.|Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.|Hubei Clinical Cancer Study Centre, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Zhou
mesh_terms: D000072283:A549 Cells; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D015153:Blotting, Western; D002216:Captopril / Q000494:pharmacology*; D002478:Cells, Cultured; D005355:Fibrosis / Q000188:drug therapy* / Q000209:etiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014965:X-Rays / Q000009:adverse effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D002216:Captopril
keywords: EA.Hy926; NF-κB; TGF-β1; captopril; irradiation