文章摘要

白细胞介素13对胆管成纤维细胞TGF-β1/Smads通路表达的影响及地塞米松的干预作用

作者: 1李克跃, 1石承先, 1汤可立, 1魏国微, 1刘振华, 1黎涛, 1张帅民, 1徐贤刚
1 贵州省人民医院 肝胆外科,贵州 贵阳 550002
通讯: 李克跃 Email: keyuelee@sohu.com
DOI: 10.3978/.10.3978/j.issn.1005-6947.10.3978/j.issn.1005-6947.2017.08.006
基金: 贵州省科学技术厅—贵州省人民医院联合基金资助项目, 黔科合LH字[2016]7146

摘要

目的:探讨白细胞介素13(IL-13)对胆管成纤维细胞转化生长因子β1(TGF-β1)/Smads通路活性的影响及地塞米松(Dex)的干预作用。方法:分离、培养兔胆管成纤维细胞并鉴定后分别给予IL-13、IL-13联合不同浓度的Dex(0.01、0.05、0.25 mg/mL)干预48 h,以无处理的胆管成纤维细胞为空白对照,分别用CCK-8细胞计数法测定各组细胞增殖水平;real-time PCR检测各组细胞TGF-β1、Smad3及Smad4基因mRNA表达;Western blot检测各组细胞TGF-β1及Smad4蛋白表达。结果:与空白对照组比较,在IL-13干预48 h后,胆管成纤维细胞增殖明显加速、TGF-β1、Smad3及Smad4 mRNA表达均明显上调,TGF-β1、Smad4蛋白表达明显上调(均P<0.05),而Dex对IL-13引起的上述变化有明显的抑制作用,并呈一定的浓度依赖趋势(部分P<0.05)。结论:IL-13能增加胆管成纤维细胞TGF-β1/Smads通路的活性,削弱该通路的活化可能是Dex抑制良性胆道狭窄形成的机制之一。
关键词: 胆道 缩窄 病理性 成纤维细胞 Smad蛋白质类 白细胞介素13 地塞米松

Influence of interleukin 13 on activity of TGF-β1/Smads signaling pathway in bile duct fibroblasts and the interventional effect of dexamethasone

Authors: 1LI Keyue, 1SHI Chengxian, 1TANG Keli, 1WEI Guowei, 1LIU Zhenhua, 1LI Tao, 1ZHANG Shuaimin, 1XU Xiangang
1 Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang 550002, China

CorrespondingAuthor:LI Keyue Email: keyuelee@sohu.com

Abstract

Objective: To investigate the influence of interleukin 13 (IL-13) on activity of transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in bile duct fibroblasts and the interventional effect of dexamethasone (Dex). Methods: Rabbit bile duct fibroblasts were isolated and cultured and then identified. Then, the bile duct fibroblasts were exposed to IL-13 or IL-13 plus different concentrations (0.01, 0.05 and 0.25 mg/mL) of Dex respectively for 48 h, using untreated bile duct fibroblasts as blank control. Afterwards, cell proliferation was assessed by CCK-8, the mRNA expressions of TGF-β1, Smad3 and Smad4 were determined by real-time PCR and the protein expressions of TGF-β1 and Smad4 were examined by Western blot. Results: In bile duct fibroblasts after exposure to IL-13 for 48 h, the cell proliferation was significantly increased, the mRNA expressions of TGF-β1, Smad3 and Smad4 and the protein expressions of TGF-β1 and Smad4 were significantly up-regulated (all P<0.05), and the above changes exerted by IL-13 were significantly inhibited by Dex addition in a certain concentration-dependent manner (part P<0.05). Conclusion: IL-13 can enhance the activity of TGF-β1/Smads pathway in bile duct fibroblasts, and weakening the activation of this signaling pathway may be one of the mechanisms of the inhibitory effect of Dex on benign biliary stricture.
Keywords: Biliary Tract Constriction Pathologic Fibroblasts Smad Proteins Interleukin-13 Dexamethasone