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Effect of IL-33/TLR4 signal pathway in inducing A549 cells transition to mesenchymal cells from epithelium in vitro |
LIU Chao, ZHENG Jin-xu, XU Jiao, ZHU Qin, DU Chuan-chong |
(Department of Respiratory Medicine, the Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001, China) |
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Abstract Objective: To investigate the role and mechanism of IL-33 in the process of turning epithelium-mesenchyme for A549 cells which is in one strain of human alveolar epithelial cells. Methods: To stimulate cultured A549 cells with TGF-β1(5 ng/mL). MTT assay was used to assess the proliferation of the A549 cells in response to TGF-β1 treatment the dynamic expressions of IL-33/TLR4 mRNA were detected by RT-PCR. Western blotting were employed to examine the mRNA and protein expressions of α-smooth muscle actin (α-SMA) and E-cad, p-AKT. Results: The data showed that TGF-β1 had no obvious effects on the proliferation of A549 cells. Stimulated by TGF-β1,E-cad expression of A549 cells gradually declined. αSMA expression was higher. p-AKT expression gradually increased. Real-time PCR had shown that expressions of IL-33/TLR4 mRNA increased firstly then decreased gradually. The significant differences were observed from 0 h to 24 h, especially on 24 h,compared with control group(P<0.05). Conclusion: IL-33/TLR4/PI3K/AKT signal transduction pathway promoted epithelialmesenchymal transition (EMT) of A549, especially on earlier inflammatory reaction.
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Received: 24 March 2014
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[1]Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis[J]. NEJM, 2001, 345(7): 517-525.[2]Kalluri R. EMT: when epithelial cells decide to become mesenchymallike cells[J]. J Clin Invest, 2009,119(6): 1417-1419.[3]吴立艳, 郑金旭, 宋萍, 等. IL-33 参与促进 A549 细胞上皮间质转化及作用机制[J]. 中国现代医学杂志, 2013, 23(21): 8-13.[4]许姣, 刘超, 郑金旭, 等. IL-33 在肺纤维化小鼠的表达[J]. 江苏医药, 2013,39( 4): 373-375.[5]郑金旭, 汤艳, 黄振杰, 等. 热休克蛋白 47 参与 TGF-β1 促人胚肺细胞胶原合成[J]. 基础医学与临床, 2011, 31(9): 965-969.[6]马文东, 袁媛, 杨奕, 等. TGF-β1 介导的 RhoA/ROCK 通路在大鼠肺肌成纤维细胞分化中的调节作用[J]. 中国病理生理杂志, 2013, 29(10): 1758-1763.[7]李远清, 彭晖, 吴超, 等. 高糖通过转化生长因子 β 信号诱导肾小球内皮细胞向肌成纤维细胞转分化[J]. 中华肾脏病杂志, 2012, 28(12): 950-955.[8]郑金旭, 张小燕, 端礼荣, 等. 转化生长因子-β1诱导 A549 细胞向间充质细胞转化的作用研究[J]. 江苏大学学报: 医学版, 2008, 18(4): 327-329.[9]Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines[J]. Immunity, 2005, 23(5): 479-490.[10]KurowskaStolarska M, Stolarski B, Kewin P, et al. IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation[J]. J Immunol, 2009, 183(10): 6469-6477. [11]刘含智,杨红振,米粟,等.Toll样受体2介导博莱霉素诱导的急性肺损伤、炎症与纤维化[J].药学学报,2010,45(8):976-986.[12]Seki E, Park E, Fujimoto J. Toll-like receptor signaling in liver regeneration, fibrosis and carcinogenesis[J]. Hepatol Res, 2011, 41(7): 597-610.[13]Lombardo E, Alvarez-Barrientos A, Maroto B, et al. TLR4-mediated survival of macrophages is MyD88 dependent and requires TNFα autocrine[J].J Immunol,2007,178(6):3731-3739.[14]苏海英. TLR4/PI3K 信号相关分子在气道上皮细胞诱导的哮喘气道平滑肌细胞迁移中的作用及机制研究[D]. 桂林:桂林医学院, 2011. |
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