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IL-17 A对系统性硬化病小鼠模型皮肤和肺部纤维化病变的作用

Effects of IL-17A on fibrosis of skin and lung in a mouse model of systemic sclerosis
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摘要 目的 研究白细胞介素(IL)-17A在博莱霉素(BLM)致系统性硬化病(SSc)小鼠模型中的表达及对皮肤、肺部炎症和纤维化病变的作用.方法 24只雌性BALB/c小鼠随机分为4组,包括正常对照组(小鼠背部皮下注射磷酸盐缓冲液)、模型组(小鼠背部皮下注射BLM)、抗体组(BLM+抗IL-17A单克隆抗体)、同型对照组(BLM+同型对照).观察各组小鼠背部注射部位皮肤和肺部的病理改变、炎症和纤维化评分,免疫组化和实时荧光定量PCR(RT-PCR)检测小鼠皮肤和肺部的IL-17A、TGF-β1、Ⅰ型胶原mRNA的表达.体外培养小鼠肺成纤维细胞(FB),分别加入IL-17A细胞因子和单克隆抗体,检测各组细胞Ⅰ型胶原mRNA、TGF-β1 mRNA的表达,酶联免疫吸附试验(ELISA)检测培养液上清IL-6、TGF-β1的水平.结果 (1)抗体组小鼠皮肤厚度、皮肤炎症、肺组织炎症和纤维化评分明显低于模型组及同型对照组(P<0.05).(2)免疫组化提示模型组IL-17A在皮肤和肺组织的表达明显高于正常对照组,抗体组皮肤和肺组织IL-17A蛋白的表达均低于模型组和同型对照组(P<0.05).(3)模型组IL-17A mRNA在皮肤和肺组织的表达明显高于正常对照组,抗体组小鼠皮肤和肺组织中IL-17A、TGF-β1、Ⅰ型胶原mRNA的表达均低于模型组和同型对照组(P<0.05).(4)体外细胞培养SSc小鼠肺FB,IL-17A单克隆抗体阻断组TGF-β1、Ⅰ型胶原mRNA水平、 细胞上清液IL-6、TGF-β1水平均低于IL-17A细胞因子刺激组(P<0.05),而均高于对照组(P<0.05).结论 IL-17A可促进SSc小鼠模型皮肤和肺脏炎症和纤维化的发展,阻断IL-17A可能通过抑制TGF-β1、IL-6和Ⅰ型胶原的产生进而抑制SSc纤维化病变. Objective To analyze the expression of interleukin ( IL)-17A in a mouse model of bleomycin ( BLM)-induced systemic sclerosis ( SSc) and to evaluate its effects on inflammation and fibrosis in skin and lung tissues. Methods Twenty-four female BALB/c mice were randomly divided into four groups:normal control group ( mice were subcutaneously injected with phosphate buffer ) , model group (subcutaneously injected with BLM), antibody group (injected with BLM + IL-17A monoclonal antibody), homotypic control group ( injected with BLM + isotype control) . Pathological changes in skin and lung tis-sues of those mice were observed;inflammatory and fibrotic scores were assessed. Immunohistochemistry and real-time fluorescent quantitative PCR ( RT-PCR) were used to detect the expression of IL-17A, TGF-β1 and typeⅠ collagen in skin and lung tissues of those mice at mRNA level. Mouse lung fibroblasts ( FB) de-rived from the mice of model group were cultured in vitro and then were cultured with IL-17A cytokines with or without the interference of monoclonal antibodies. Expression of typeⅠ collagen and TGF-β1 at mRNA level and levels of IL-6 and TGF-β1 in the culture supernatants were detected by RT-PCR and enzyme-linkedimmunosorbent assay ( ELISA) , respectively. Results Compared with the mice of model and homotypic control groups, those of the antibody group showed mild skin thickening, skin inflammation and lung inflam-mation as well as lower fibrosis scores (P<0. 05). The expression of IL-17A at both protein and mRNA lev-els and the expression of TGF-β1 and collagen typeⅠat mRNA level in skin and lung tissues of mice of the antibody group were significantly lower than those of the model and homotypic control group (P<0. 05). Re-sults of the in vitro cell culture of SSc mice-derived lung FB with IL-17A showed that the expression of TGF-β1 and typeⅠ collagen at mRNA level and the levels of IL-6 and TGF-β1 in the culture supernatants were decreased wi
作者 黄舒柠 雷玲 赵铖 王旭 文静 覃芳 Huang Shu-ning, Lei Ling, Zhao Cheng, Wang Xu, Wen Jing, Qin Fang (1.Department of Rheumatology and Immunology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China ; 2.Department of Rheumatology and Immunology, People's Hospital of Zhengzhou, Zhengzhou 450003, China )
出处 《中华微生物学和免疫学杂志》 CAS CSCD 北大核心 2017年第2期105-111,共7页 Chinese Journal of Microbiology and Immunology
基金 广西自然科学基金项目(2016GXNSFAA380175)
关键词 系统性硬化病 抗白细胞介素17A单克隆抗体 转化生长因子Β1 Ⅰ型胶原 TGF-β1 IL-17A Systemic sclerosis Anti-IL-17A monoclonal antibody IL-17A TypeⅠcollagen
作者简介 通信作者:雷玲,Email:leiling1972@aliyun.com,电话:0771-3277232
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