Anti-inflammatory effect of 1α,25-dihydroxyvitamin D3 in human coronary arterial endothelial cells: Implication for the treatment of Kawasaki disease

Anti-inflammatory effect of 1α,25-dihydroxyvitamin D3 in human coronary arterial endothelial cells: Implication for the treatment of Kawasaki disease
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DOI:
10.1016/j.jsbmb.2008.12.004
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发表时间:
2009-01-01
影响因子:
4.1
通讯作者:
Furukawa, Susumu
Furukawa, Susumu
中科院分区:
生物学2区
文献类型:
--
作者:
Suzuki, Yasuo;Ichiyama, Takashi;Furukawa, Susumu

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川崎(KD)是一种与炎性细胞因子相关的儿童急性发热性血管炎,其中血管炎症导致冠状动脉损伤。维生素D的活性形式,1 α,25-二羟基维生素D-3(1 α,25-(OH)(2)D-3)表现出抗炎活性。本研究采用RT-PCR和Western blotting方法分别检测了人冠状动脉内皮细胞(HCAEC)维生素D受体mRNA和蛋白的表达。我们通过ELISA检测了1 α,25-(OH)(2)D-3是否抑制肿瘤坏死因子-α(TNF-α)诱导的核转录因子-κ B(NF-κ B)的活化,NF-κ B对HCAEC中促炎细胞因子的表达至关重要。此外,我们通过流式细胞术测定了1 α,25-(OH)(2)D-3对HCAEC中TNF-α诱导的E-选择素表达的抑制作用。RT-PCR显示HCAEC中存在维生素D受体mRNA。Western blotting证实HCAEC中存在维生素D受体蛋白。ELISA结果显示,1 α,25-(OH)(2)D-3预处理可显著抑制TNF-α诱导的HCAEC中NF-κ B活化。流式细胞术显示1 α,25-(OH)(2)D-3预处理显著抑制TNF-α诱导的HCAEC上E-选择素的表达。我们的研究结果表明,1 α,25-(OH)(2)D-3可能调节KD血管炎的炎症反应。(C)2008爱思唯尔有限公司保留所有权利。
Kawasaki disease (KD) is an acute febrile vasculitis in childhood that is associated with inflammatory cytokines, in which the vascular inflammation results in damage to the coronary arteries. The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D-3 {1 alpha,25-(OH)(2)D-3) exhibits anti-inflammatory activities. In this study, we determined the mRNA and protein expression of the vitamin D receptor in human coronary arterial endothelial cells (HCAEC) by RT-PCR and Western blotting, respectively. We examined whether or not 1 alpha,25-(OH)(2)D-3 inhibits the tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear transcription factor-kappa B (NF-kappa B), which is essential for the expression of proinflammatory cytokines in HCAEC, by ELISA. In addition, we determined the inhibitory effect of 1 alpha,25-(OH)(2)D-3 on E-selectin expression induced by TNF-alpha in HCAEC by flow cytometry. RT-PCR revealed mRNA for the vitamin D receptor in HCAEC. Western blotting demonstrated vitamin D receptor protein in HCAEC. ELISA showed that pretreatment with 1 alpha,25-(OH)(2)D-3 significantly inhibited the TNF-alpha-induced NF-kappa B activation in HCAEC. Moreover, flow cytometry revealed that pretreatment with 1 alpha,25-(OH)(2)D-3 significantly inhibited the TNF-alpha-induced expression of E-selectin on HCAEC. Our results suggest that adjunctive 1 alpha,25-(OH)(2)D-3 may modulate the inflammatory response during KD vasculitis. (C) 2008 Elsevier Ltd. All rights reserved.