Toll样受体2介导的分子信号途径对婴幼鼠巨噬细胞产生细胞因子的影响

摘要

Objective To investigate the mechanism of the cytokine production in infant mice of pertinent macrophage and the function of TLR2-mediated signaling in it.Methods 1.Resident peritoneal macrophages from infant and adult mouse were obtained by peritoneal lavage. 2.Measurements of cytokine levels by ELISA. 3.Analysis of TLRs expression by flow cytometry. 4.The P38 MAPK and ERK1/2 were detected by Western blotting.Results 1.Infant macrophages produced decreased levels of TNF-α and IL-6 after stimulation with TLR2 ligands. 2.TLR2 expression was not altered in infant macrophages. 3.Zymosan-stimulated activation of P38 MAPK and ERK1/2 was reduced in infant macrophage. 4.Levels of TNF-α and IL-6 after stimulation with TLR2 ligands was not altered in infant macrophages (WT and TLR2-/- compared); but there is difference in adult macrophages (WT and TLR2-/- compared).Conclusion Defi cient TLR2-mediated signaling in infant macrophages may contribute to the susceptibility of infants to bacterial infection.%目的：探讨婴幼鼠巨噬细胞产生细胞因子功能减弱的分子机制，尤其是Toll样受体2（TLR2）在其中的作用。方法1.腹膜灌洗法分离小鼠腹腔巨噬细胞。2.ELISA法测定细胞因子TNF-α和IL-6。3.流式细胞仪分析细胞TLRs的表达。4.蛋白印迹法（Western blotting）测定信号传导分子P38 MAPK和ERK1/2。结果1.TLR2激动剂酵母提取物刺激后婴幼鼠腹腔巨噬细胞释放细胞因子与成年鼠比较显著减少。2.婴幼鼠与成年鼠腹腔巨噬细胞表面表达的TLR2量差异无统计学意义。3.TLR2激动剂酵母提取物刺激后婴幼鼠腹腔巨噬细胞中信号传导分子P38 MAPK及ERK1/2与成年鼠比较显著减少。4.酵母提取物分别刺激野生型婴幼鼠和成年鼠腹腔巨噬细胞及TLR2-/-型婴幼鼠和成年鼠腹腔巨噬细胞，发现婴幼鼠细胞因子水平差异无统计学意义（野生型和TLR2-/-型比较），成年鼠细胞因子水平差异有统计学意义（野生型和TLR2-/-型比较）。结论 TLRs介导的信号途径缺陷导致婴幼鼠对细菌感染的敏感性增强。