IL-16通过促进巨噬细胞的M1型极化加重葡聚糖硫酸钠诱导的小鼠炎症性肠病  

IL-16 aggravates dextran sulfate sodium( DSS )-induced mouse inflammatory bowel disease by promoting M1 polarization of macrophages

作　　者：朱玉贞 戴军[2] 姚潇颖 董冠军[2] 张惠[2] 闫风连[2] 李春霞[2] 李学慧 熊化保 司传平[2] ZHU Yuzhen;DAI Jun;YAO Xiaoying;DONG Guanjun;ZHANG Hui;YAN Fenglian;LI Chunxia;LI Xuehui;XIONG Huabao;SI Chuanping(Department of Immunology,Basic Medical School,Qingdao University,Qingdao 266071;Institute of Immunology and Molecular Medicine,Jining Medical University,Jining 272067,China;Department of Medicine,Immunology Institute,Icahn School of Medicine at Mount Sinai,New York,NY 10029,USA)

机构地区：[1]青岛大学基础医学院免疫学系,山东青岛266071 [2]济宁医学院免疫学与分子医学研究所,山东济宁272067 [3]美国纽约州西奈山伊坎医学院免疫学研究所医学系,纽约10029

出　　处：《细胞与分子免疫学杂志》2018年第8期695-701,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：山东省自然科学基金(ZR2013HL014)

摘　　要：目的研究白细胞介素16(IL-16)在炎症性肠病(IBD)发生发展过程中的作用并且明确其参与IBD发病的调控机制。方法采用7周龄野生型C57BL/6(WT)和IL-16敲除(IL-16^(-/-))雌性小鼠,分为WT对照组、WT葡聚糖硫酸钠(DSS)处理组、IL-16^(-/-)对照组和IL-16^(-/-)DSS处理组。DSS模型组给予含25 g/L DSS的饮水7 d,建立IBD模型,对照组小鼠给予正常饮水,建模期间记录小鼠体质量绘制体质量变化曲线。7 d后,解剖分离小鼠全结肠,反转录PCR检测结肠组织IL-16 mRNA水平,ELISA检测结肠组织IL-16蛋白水平,免疫荧光技术检测结肠组织IL-16的表达和定位。HE染色检测小鼠结肠病理损伤,原位末端转移酶标记技术(TUNEL)检测结肠组织细胞凋亡,流式细胞术检测腹腔细胞中巨噬细胞的数量和极化情况(F4/80、CD86),免疫组织化学染色法检测结肠组织中巨噬细胞的分布,反转录PCR分别检测结肠组织IL-6、IL-12 mRNA水平,ELISA检测IL-6、IL-12蛋白水平。结果 DSS诱导后,结肠组织高表达IL-16。与WT DSS处理组相比,IL-16^(-/-)DSS处理组小鼠体质量变化较小,结肠组织损伤较轻,凋亡细胞显著减少,IL-16^(-/-)小鼠腹腔或结肠组织中巨噬细胞显著减少,巨噬细胞向M1亚型的极化水平明显减弱,其标志性炎性因子IL-6、IL-12的水平显著降低。结论 IL-16可通过促进巨噬细胞的M1型极化加重DSS诱导的炎症性肠病。Objective To investigate the role of interleukin-16(IL-16)in the development of inflammatory bowel disease (IBD)and clarify its regulatory mechanism involved in the pathogenesis of IBD.Methods Seven-week-old wild-type C57BL/6 (WT)and IL-16knockout (IL-16^-/-)female mice were divided into WT control group,WT dextran sulfate sodium (DSS) treatment group,IL-16^-/-control group and IL-16^-/-DSS treatment group.The DSS model groups were given the water with 25g/L DSS for 7 days to establish the IBD models,while the control groups were given the normal water.During the modeling period,the body mass of mice was recorded to calculate the body mass curve.After 7 days,the whole colon of the mice was dissected and the level of IL-16 mRNA in the colon tissue was detected by real-time PCR.The level of IL-16protein in the colon tissue was detected by ELISA.The expression and localization of IL-16 in the colon tissue were observed by immunofluorescence technique.HE staining was used to detect colonic pathological injury in mice.TUNEL assay was used to detect cell apoptosis of the colon tissue.Flow cytometry was used to detect the number and polarization of macrophages in peritoneal cells (F4/80,CD86).Immunohistochemical staining was used to detect the distribution of macrophages in the colon tissues.Real-time PCR was used to detect IL-6 and IL-12 mRNA levels in the colon tissue,and IL-6 and IL-12 protein levels were detected by ELISA.Results DSS induced high expression of IL-16 in the colon tissue.Compared with WT DSS treatment group,IL-16^-/-DSS treatment group showed less changes in body mass,less colon tissue damage,and markedly lower percents of apoptotic cells in the peritoneal or colonic tissues of IL-16^-/-mice.What's more,the number of macrophages,the polarization level of M1 macrophages,and the levels of the iconic inflammatory factors IL-6 and IL-12 significantly decreased in IL-16^-/-DSS treatment group compared with WT DSS treatment group.Conclusion IL-15 can aggravate DSS-induced IBD by promoting the polarization o

关 键 词：白细胞介素16(IL-16) 巨噬细胞 极化 炎症性肠病(IBD) 

分 类 号：R392.12[医药卫生—免疫学] R364.5[医药卫生—基础医学]