Budesonide reduces vascular endothelial growth factor secretion and expression in airway (Calu-1) and alveolar (A549) epithelial cells
Budesonide reduces vascular endothelial growth factor secretion and expression in airway (Calu-1) and alveolar (A549) epithelial cells
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DOI：
10.1016/s0014-2999(01)01192-x
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发表时间：
2001-08-10
影响因子：
5
通讯作者：
Kompella, UB
中科院分区：
文献类型：
--
作者：
Bandi, N;Kompella, UB
血管内皮生长因子（VEGF）是一种在呼吸道上皮细胞中表达的细胞因子，可诱导血管通透性过高和水肿，这些症状可通过布地奈德（一种抗哮喘皮质类固醇）缓解。然而，布地奈德在呼吸道上皮中对VEGF水平的调节尚未研究。在这项研究中，我们研究了在人气道（Calu-1）和肺泡（A549）上皮细胞中使用布雷菲德菌素A和莫能菌素的VEGF分泌机制，并进一步确定布地奈德是否通过糖皮质激素受体介导的机制抑制VEGF分泌和mRNA表达。在这两种细胞类型中，VEGF分泌被布雷菲德菌素A和莫能菌素抑制，提示VEGF通过内质网（ER）-高尔基体途径的囊泡转运。在没有细胞毒性的浓度下，布地奈德减少了两种细胞类型中的VEGF分泌和VEGF mRNA表达，并且这些作用被糖皮质激素受体拮抗剂米非司酮（RU 486）抑制，表明布地奈德通过其糖皮质激素受体介导的作用减少VEGF分泌和表达。此外，布地奈德介导的VEGF mRNA的抑制是时间和蛋白质合成依赖性的。因此，布地奈德可能在治疗与VEGF升高相关的呼吸道疾病方面具有潜在价值。(C)2001 Elsevier Science B. V.保留所有权利。
Vascular endothelial growth factor (VEGF), a cytokine expressed in the respiratory epithelial cells, induces vascular hyperpermeability and edema, symptoms that are alleviated by budesonide, an anti-asthma corticosteroid. However, modulation of VEGF levels by budesonide in the respiratory epithelium has not been studied. In this study, we investigated the mechanisms of VEGF secretion using brefeldin A and monensin in human airway (Calu-1) and alveolar (A549) epithelial cells, and further determined whether budesonide inhibits VEGF secretion and mRNA expression through a glucocorticoid receptor-mediated mechanism, In both cell types, VEGF secretion was inhibited by brefeldin A and monensin, suggesting vesicular transport of VEGF through endoplasmic reticulum (ER)-golgi pathway. At concentrations devoid of cytotoxicity, budesonide reduced VEGF secretion and VEGF mRNA expression in both cell types and these effects were inhibited by mifepristone (RU 486), a glucocorticoid receptor antagonist, suggesting that budesonide reduces VEGF secretion and expression through its glucocorticoid receptor-mediated action. Also, budesonide-mediated inhibition of VEGF mRNA was time- and protein synthesis-dependent. Thus, budesonide may be of potential value in treating disorders of the respiratory tract that are associated with VEGF elevation. (C) 2001 Elsevier Science B.V. All rights reserved.