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目的探讨支气管哮喘白介素4/白介素4受体(IL-4/IL-4R)通路过度活化与转录因子STAT4和STAT6表达的关系。方法2007年2—10月,对重庆医科大学附属儿童医院收治的25例哮喘患儿通过RT-PCR、IF和ELISA方法,检测经过抗人IL-4R单克隆抗体(mhIL-4RAb)干预前后外周血淋巴细胞中STAT4和STAT6 mRNA的表达、pSTAT4和pSTAT6表达量的变化及培养上清液中IL-4和γ干扰素(IFN-γ)质量浓度。并对同期体检的30名对照组儿童进行同样检测。结果(1)对哮喘组、干预组和对照组患儿淋巴细胞培养上清液中IL-4及IFN-γ水平分别进行比较,哮喘组与后两组差异有统计学意义(均P<0.05);后两组之间差异无统计学意义(P>0.05)。(2)对3组淋巴细胞中STAT4 mRNA、STAT6 mRNA表达进行比较:哮喘组STAT4 mRNA表达量显著低于后两组,STAT6 mRNA表达则显著高于后两组(均P<0.05),后两组间比较差异无统计学意义(P>0.05)。(3)免疫荧光显示哮喘组淋巴细胞中pSTAT4表达显著低于后两组(均P<0.05);pSTAT6表达水平则显著提高,后两组间比较差异无统计学意义(P>0.05)。结论阻断哮喘患儿IL-4/IL-4R通路能够通过影响pSTAT4和pSTAT6的表达影响IL-4和IFN-γ的分泌,从而扭转Th2细胞分化亢进的状态。pSTAT4和pSTAT6的表达之间存在相互拮抗。IL-4及IFN-γ分泌量的变化可以反向影响STAT6及STAT4的转录。
Objective To investigate the relationship between interleukin-4 / interleukin-4 receptor (IL-4 / IL-4R) pathway overexpression and the expression of STAT4 and STAT6 in bronchial asthma. Methods From January to October 2007, 25 cases of asthmatic children admitted to Children’s Hospital of Chongqing Medical University were detected by RT-PCR, IF and ELISA methods before and after intervention with anti-human IL-4R monoclonal antibody (mhIL-4RAb) The expression of STAT4 and STAT6 mRNA, the expression of pSTAT4 and pSTAT6 in blood lymphocytes and the concentration of IL-4 and IFN-γ in the culture supernatant were measured. The same test was performed on 30 control children in the same period. Results (1) The levels of IL-4 and IFN-γ in the supernatant of lymphocytes in the asthmatic group, the intervention group and the control group were respectively compared with those in the asthmatic group and the latter two groups (all P <0.05 ). There was no significant difference between the two groups (P> 0.05). (2) The STAT4 mRNA and STAT6 mRNA expression in the three groups of lymphocytes were compared: STAT4 mRNA expression in asthma group was significantly lower than the latter two groups, STAT6 mRNA expression was significantly higher than the latter two groups (all P <0.05) There was no significant difference between the two groups (P> 0.05). (3) Immunofluorescence showed that the expression of pSTAT4 in lymphocytes in asthmatic group was significantly lower than that in the latter two groups (all P <0.05); pSTAT6 expression was significantly increased in the asthmatic group (P> 0.05). Conclusion Blocking the IL-4 / IL-4R pathway in asthmatic children can affect the secretion of IL-4 and IFN-γ by affecting the expression of pSTAT4 and pSTAT6, thus reversing the state of Th2 cell hyper-differentiation. There is mutual antagonism between the expression of pSTAT4 and pSTAT6. The changes of IL-4 and IFN-γ secretion can reversely affect the transcription of STAT6 and STAT4.