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TIM-1对哮喘小鼠气道MUC5AC及Th2细胞因子表达的影响
强丽霞1,金寿德2,唐昊1,李兵1,修清玉1,石昭泉1*
0
(1. 第二军医大学长征医院呼吸内科,上海 200003
2. 哈尔滨医科大学附属第四医院呼吸内科,哈尔滨 150001
*通信作者)
摘要:
目的 研究T细胞免疫球蛋白-黏蛋白-1(TIM-1)表达对哮喘小鼠气道MUC5AC及Th2细胞因子的作用,探讨气道黏液高分泌的机制。方法 30只健康雌性C57BL/6小鼠,按随机数字表法分为正常、哮喘模型组(哮喘组)和哮喘模型+TIM-1抗体处理组(TIM-1抗体组),每组10只。检测小鼠外周血单个核细胞(PBMCs)TIM-1+细胞比例、气道MUC5AC mRNA表达、肺泡灌洗液(BALF)中IL-13、IL-4、IL-5水平及黏液细胞数量和细胞体积的改变。结果 (1)哮喘组及TIM-1抗体组小鼠外周血PBMCs中TIM-1+ 细胞比例(11.20%,5.11%)均高于正常组(0.64%,P<0.05),且TIM-1抗体组低于哮喘组(P<0.05)。(2)哮喘组及TIM-1抗体小鼠气道黏液细胞MUC5AC mRNA相对表达(17.3±1.4,5.6±0.3)及IL-13[(16.80±0.63) ng/ml,(5.70±0.64)ng/ml]、IL-4[(614.72±117.39) pg/ml,(325.78±86.54) pg/ml]、IL-5[(1 681.13±613.55) pg/ml,(513.42±86.87) pg/ml]水平均高于正常组[1, (1.09±0.25) ng/ml,(17.56±3.01) pg/ml,(30.78±9.67) pg/ml],TIM-1抗体组小鼠上述指标低于哮喘组(P<0.05)。(3)气道MUC5AC及IL-13表达与TIM-1+细胞表达均呈正相关(r1=0.946,P1=0.004; r2=0.984,P2=0.000)。 结论 哮喘小鼠外周血TIM-1+细胞升高,可致气道黏液过度分泌;抑制TIM-1表达可减少哮喘气道黏液高分泌。调节TIM-1表达有可能成为减少黏液高分泌及治疗哮喘的新途径。
关键词:  T细胞免疫球蛋白-黏蛋白-1  MUC5AC  Th2细胞因子  哮喘
DOI:10.3724/SP.J.1008.2012.00581
投稿时间:2012-02-20修订日期:2012-04-27
基金项目:国家自然科学基金(30670912),上海市自然科学基金(11ZR1448600).
Effect of T cell Ig and mucin 1 on expression of MUC5AC and Th2 cytokine in airway of asthmatic mice
QIANG Li-xia1,JIN Shou-de2,TANG Hao1,LI Bing1,XIU Qing-yu1,SHI Zhao-quan1*
(1. Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
2. Department of Respiratory Medicine, Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China
*Corresponding author.)
Abstract:
Objective To investigate the effect of T cell Ig and mucin 1 (TIM-1) on MUC5AC and Th2 cytokine expression in the airway of asthmatic mice, so as to understand the mechanism of airway mucus hypersecretion.Methods Thirty healthy female C57BL/6 mice were randomly divided into control,asthmatic and TIM-1 mAb treated groups, with 10 mice in each group. The proportion of TIM-1 positive cells in peripheral blood mononuclear cells (PBMCs), MUC5AC mRNA expression in the airway, levels of IL-13, IL-4 and IL-5 in bronchoalveolar lavage fluid (BALF), and the number and volume of airway mucous cells were examined in the three groups. Results The proportions of PBMCs TIM-1 positive cells in asthmatic(11.20%) and TIM-1 mAb treated (5.11%) mice were significantly higher than that in the control group (0.64%, P<0.05), and that in TIM-1 mAb treated mice was significantly lower than that in the asthmatic mice (P<0.05). (2) MUC5AC mRNA expression in the airway mucous cells in the asthmatic (17.3±1.4) and TIM-1 mAb treated (5.6±0.3) mice were significantly higher than that in control mice (P<0.05). The BALF levels of IL-13 (ng/ml), IL-4 (pg/ml), and IL-5 (pg/ml) were 16.80±0.63, 614.72±117.39, and 1 681.13±613.55 in the asthmatic, and were 5.70±0.64, 325.78±86.54, and 513.42±86.87 in TIM-1 mAb treated mice, respectively, which were all significantly higher than those in the control mice ([1.09±0.25] ng/ml for IL-13, [17.56±3.01] pg/ml for IL-4, and [30.78±9.67] pg/ml for IL-5, P<0.05). And all the above parameters in the TIM-1 mAb treated mice were significantly lower than those in the asthmatic mice (P<0.05). (3) MUC5AC and IL-13 expression in the airway was positively correlated with TIM-1 positive cells in asthmatic mice (r1=0.946, P1=0.004; r2=0.984, P2=0.000). Conclusion TIM-1 positive cells are increased in PBMCs in asthmatic mice, which can result in airway mucous cell metaplasia and mucus hypersecretion. Inhibition of TIM-1 expression can reduce mucus hypersecretion. Regulation of TIM-1 might be a novel approach for asthma treatment.
Key words:  T cell Ig and mucin 1  MUC5AC  Th2 cytokines  asthma