YKL-40调控支气管上皮分泌IL-8对支气管平滑肌细胞增殖和迁移的影响  

YKL-40-induced IL-8 expression from bronchial epithelium leads to bronchial smooth muscle proliferation and migration

作　　者：肖琳[1] 石昭泉[1] 李兵[1] 修清玉[1] 唐昊[1] 

机构地区：[1]上海长征医院呼吸内科,上海200003

出　　处：《中国免疫学杂志》2014年第12期1591-1595,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(No.81370137);2013年度上海市卫生系统优秀学科带头人培养计划项目(No.XYQ2013075)的资助

摘　　要：目的:研究YKL-40介导支气管上皮细胞的炎症反应及对支气管平滑肌细胞增殖和迁移的影响。方法:体外培养支气管上皮永生细胞系(BEAS-2B)和原代人支气管上皮细胞(HBECs),用不同浓度的YKL-40刺激BEAS-2B和HBECs不同时间后,用Realtime PCR和ELISA方法检测炎症细胞因子的变化。YKL-40刺激BEAS-2B和HBECs 6 h后,更换新鲜培养基继续培养18 h后收集细胞培养液,命名为(YKL-40-BEAS-2B-CM、YKL-40-HBECs-CM),用于培养支气管平滑肌细胞(BSMCs)。24 h后检测BSMCs迁移能力的变化,72 h后检测BSMCs增殖能力的变化。结果:在BEAS-2B和HBECs中,YKL-40均能以浓度和时间依赖方式增强IL-8 mRNA的表达和IL-8的分泌,但对RANTES、Eotaxin,TNF-α没有影响。YKL-40-BEAS-2B-CM和YKL-40-HBECs-CM刺激BSMCs能显著增强其增殖能力和迁移能力,但去除YKL-40-BEAS-2B-CM和YKL-40-HBECs-CM中的IL-8后,则未见其可以明显提高BSMCs的增殖和迁移能力。结论:YKL-40通过调控支气管上皮表达和分泌IL-8参与了哮喘时的气道炎症反应,进一步通过影响支气管平滑肌细胞的增殖和迁移介导哮喘时的气道重构。抑制IL-8有望成为控制YKL-40介导的哮喘炎症反应和组织重构的有效干预措施。Objective：To investigate YKL-40-mediated inflammation in human bronchial epithelial cells and analyzed the soluble factors secreted by bronchial epithelial cells exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells （BSMCs）.Methods：YKL-40-induced inflammation was assayed in two human bronchial epithelial cells （BEAS-2B cell line and primary human bronchial epithelial cells ,namely HBECs）.In addition,we treated BEAS-2B cells and HBECs with YKL-40,and added the conditioned culture media （ YKL-40-BEAS-2B-CM） and （ YKL-40-HBECs-CM） to BSMCs.The proliferation and migration of BSMCs were determined by premixed WST-1 cell proliferation reagent and QCM chemotaxis migration assay ,respectively.Results： Bronchial epithelial cells treated with YKL-40 resulted in a significant increase of IL-8 production,but have no effect about RANTES ,Eotaxin and TNF-α.YKL-40-BEAS-2B-CM and YKL-40-HBECs-CM induced IL-8 was found to further stimulate proliferation and migration of BSMCs ,and the effects were inhibited after neutralizing IL-8.Conclusion：Through investigating the interaction of airway epithelium and smooth muscle ,our findings implicate that YKL-40 may be involved in the inflammation of asthma by induction of IL-8 from epithelium,subsequently contributing to BSMCs proliferation and migration.Moreover, inhibition of IL-8 signaling is a potential therapeutic target for YKL-40-induced inflammation and remodeling of asthma.

关 键 词：YKL-40 支气管上皮细胞 IL-8 支气管平滑肌细胞 

分 类 号：R392.12[医药卫生—免疫学]