TARC和MDC在日本血吸虫感染小鼠Th2应答及肝纤维化中的作用

Effects of TARC and MDC on Th2 response and liver fibrosis in mice with Schistosoma japonicum infection

目的探讨胸腺活化调节趋化因子（ thymus activation regulated chemokine, TARC）和巨噬细胞来源的趋化因子（ macrophage-derived chemokine, MDC）对日本血吸虫感染宿主Th2应答及肝脏纤维化的影响。方法建立日本血吸虫感染小鼠模型，取肠系膜淋巴结及肝脏，胞内细胞因子染色法和ELISA法检测Th2应答；实时荧光定量RT—PCR法检测TARC和MDC的mRNA表达；通过测定肝脏羟脯氨酸含量以反映其纤维化水平。结果宿主肝脏Th2应答趋势与肠系膜淋巴结一致，但感染7周时肝脏局部浸润T细胞中IL-13＋Th2约为5．3％，高于肠系膜淋巴结T细胞中IL-13＋Th2水平（3％）；肝脏羟脯氨酸含量在感染第5、7、10周分别为2．9μg／mg、5．1μg／mg和8．3μg／mg，随感染进程呈进行性加剧。感染第7周时宿主肠系膜淋巴结中的TARC和MDC的表达分别为对照组的0．5倍和0．4倍，而此时宿主肝脏中TARC和MDC的表达则显著增高，分别为对照组的12．8倍和8．2倍，并且在感染进入慢性期时仍维持较高水平，分别为对照组的3．8倍和4．4倍。结论血吸虫感染刺激宿主肝脏产生Th2类趋化因子TARC和MDC，促进Th2从外周淋巴器官向肝脏局部募集从而参与肝脏病理变化。

Objective To investigate the effects of thymus activation regulated chemokine （TARC） and macrophage-derived chemokine （ MDC ） on Th2 responses and liver fibrosis in Schistosoma japonicum infection. Methods Mice were infected by percutaneous infection with 20 cercariae of S. japonicum. The Th2 response in mesentenic lymph node（MLN） and liver was determined by intracellular cytokine staining （ICC） and ELISA. TARC and MDC mRNA level in MLN and liver were measured by quantitative real time PCR. The fibrosis was measured by the content of hepatic hydroxyproline. Results The hepatic Th2 responses were observed with similar time kinetics as those in the MLN, whereas IL-13-producing Th2 cells in the liver （5.3%） were more detectable than those in the MLN （about 3% ）. Additionally, liver fibrosis was aggravated during the S. japonicum infection. The hepatic hydroxyproline was 2.9 jxg/mg,5.1 pLg/mg and 8.3 pLg/mg at 5, 7 and 10 weeks post infection. The mRNA levels of TARC and MDC in the MLN were 0.5 and 0.4 fold of uninfected mice while those levels in liver were significantly higher and 12.8 and 8.2 fold of those in uninfected mice at 7 weeks after infection. Meanwhile TARC and MDC in the liver maintained high level of mRNA in the chronic stage and were 3.8 and 4.4 fold of those in uninfected mice, respectively. Conclusion As specific chemokines for tissue recruitment of Th2 cells, TARC and MDC may play an important role in recruiting Th2 cells to liver to cause inflammatory responses and liver fibrosis.