TLR2 mAb和TLR4 mAb对急性期溃疡性结肠炎小鼠结肠黏膜炎症因子IFN-γ、IL-4及IL-17表达的影响  

Preventive effects of TLR2 monoclonal antibodies and TLR4 monoclonal antibodies on the colonal mucosal inflammatory cytokines (IFN-γ,IL-4 and IL-17) expression in mice with DSS-induced acute ulcerative colitis

作　　者：李鹃[1] 刘懿[1] 董乐[1] 岳文杰[1] 黄剑平[1] 蒋蔚茹[1] 孙旭[1] 钟良[1] 刘杰[1] 

机构地区：[1]复旦大学附属华山医院消化科,上海200040

出　　处：《复旦学报（医学版）》2010年第3期253-258,共6页Fudan University Journal of Medical Sciences

基　　金：上海市科学技术委员会基金项目(09JC1402900)

摘　　要：目的探讨TLR2单克隆抗体(toll-like receptor 2 monoclonal antibodies,TLR2 mAb)和TLR4单克隆抗体(toll-like receptor 4 monoclonal antibodies,TLR4 mAb)对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的急性期溃疡性结肠炎(ulcerative colitis,UC)小鼠结肠黏膜的炎症因子IFN-γ、IL-4及IL-17表达的影响。方法50只雄性BALB/c小鼠分为5组(每组10只):对照组(A)、模型组(B)及TLR2 mAb干预组(C)、TLR4mAb干预组(D)、TLR2 mAb和TLR4 mAb联合干预组(E)。A组小鼠饮用蒸馏水7 d;B-E组小鼠仅饮用5%DSS水溶液7 d以产生急性期溃疡性结肠炎模型。造模开始的同时,每隔48 h分别给予C、D、E干预组小鼠以TLR2 mAb(10μg)、TLR4 mAb(10μg)、TLR2 mAb(10μg)+TLR4 mAb(10μg)腹腔内注射,A、B组给予腹腔内注射生理盐水,以观察TLR2 mAb和TLR4 mAb的干预作用。观察指标包括疾病活动指数(disease activityindex,DAI)、结肠组织病理学评分(histopathological score,HS)。造模及干预7 d后处死小鼠,Real-ti me PCR法检测各组结肠黏膜TLR2、TLR4、IFN-γ、IL-4及IL-17的mRNA表达。结果(1)与A组相比,B组小鼠肠道DAI及HS明显增高(P<0.01)。与B组相比,E组小鼠肠道DAI(P<0.05)和HS(P<0.01)均明显降低。与D组相比,E组小鼠肠道HS明显降低(P<0.05)。(2)与A组相比,B组小鼠结肠黏膜TLR2、TLR4表达明显增高(P<0.01,P<0.05)。与B组相比,C、D、E组小鼠结肠黏膜TLR2、TLR4表达均有不同程度的降低。(3)与A组相比,B组小鼠结肠黏膜IFN-γ、IL-4及IL-17的mRNA表达明显增高(P<0.01,P<0.05,P<0.01)。与B组相比,C、D、E组小鼠结肠黏膜IFN-γ、IL-4及IL-17的mRNA表达均有不同程度的降低。结论TLR2 mAb和TLR4 mAb可能通过下调小鼠结肠黏膜的炎症因子IFN-γ、IL-4、IL-17的mRNA表达而发挥其干预作用。Objective To evaluate the preventive effects of toll-like receptor 2 monoclonal antibodies（TLR2 mAb） and toll-like receptor 4 monoclonal antibodies（TLR4 mAb） on the colonal mucosal inflammatory cytokines（IFN-γ,IL-4,IL-17） expression in dextran sulfate sodium（DSS）-induced acute ulcerative colitis（UC） in mice. Methods Fifty male BALB/c mice were randomly assigned into five groups from A to E（10 for each）： the control group（group A）,the UC model group（group B）,the TLR2 mAb intervention group（group C）,the TLR4 mAb intervention group（group D）,the TLR2 mAb and TLR4 mAb intervention group（group E）.Group B to group E were given 5.0% DSS solution as drinking water for 7 days to induce acute intestinal inflammation,while group A drank distilled water freely.Groups C,D and E received TLR mAb injection intraperitoneally every 48 hours with 10 μg TLR2 mAb for the group C,with 10 μg TLR4 mAb for group D,and with 10 μg TLR2 mAb plus 10 μg TLR4 mAb for group E.Group A and B received a normal sodium injection intraperitoneally as control.Daily disease activity index（DAI） and histopathological score（HS） were evaluated.The quantities of mRNA for TLR2,TLR4,IFN-γ,IL-4 and IL-17 were determined by Real-time PCR. Results（1） Compared with group A,the DAI and HS in group B were markedly higher（P〈0.01）.Compared with group B,the DAI（P〈0.05） and HS（P〈0.01） in group E decreased.Compared with group D,the HS in group E decreased（P〈0.05）.（2） Compared with group A,TLR2 and TLR4 group B were markedly higher（P〈0.01,P〈0.05）.Compared with group B,TLR2 and TLR4 in group C to E all decreased.（3） Compared with group A,inflammatory cytokines like IFN-γ,IL-4 and IL-17 in group B were higher（P〈0.01,P〈0.05,P〈0.01）.Compared with group B,the expression of three inflammatory cytokines（IFN-γ,IL-4,IL-17） in group C to E all decreased. Conclusions TLR2 mAb and TLR4 mAb can suppress DSS-induced colitis by down-regulating the mRNA expression of i

关 键 词：溃疡性结肠炎 TLR2单克隆抗体 TLR4单克隆抗体 IFN-Γ IL-4 IL-17 

分 类 号：R574.62[医药卫生—消化系统]