JNK信号通路介导机械牵张引发的肺泡巨噬细胞炎性因子表达  

Regulation of JNK signal pathway on the expression of inflammatory cytokines in alveolar macrophages induced by mechanical stretch

作　　者：童瑾[1] 尤列.皮尔曼 维克多.科罗索夫 

机构地区：[1]重庆医科大学附属第二医院呼吸内科,重庆400010 [2]俄罗斯医学科学院远东呼吸生理与病理研究中心

出　　处：《中国老年学杂志》2011年第16期3069-3071,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金(30770951);国家自然科学基金中俄合作项目(81011120108)

摘　　要：目的观察不同机械牵张应力对大鼠肺泡巨噬细胞白介素-6(IL-6)和巨噬细胞炎症蛋白-2(MIP-2)的影响,并探讨C-JUN氨基末端激酶(JNK)对机械牵张诱导的大鼠肺泡巨噬细胞IL-6和MIP-2表达的调控作用。方法采用支气管肺泡灌洗的方法取得大鼠肺泡巨噬细胞,并建立体外大鼠肺泡巨噬细胞梯度应力的机械牵张模型,应用RT-PCR和Western印迹方法观察IL-6和MIP-2的表达。进一步应用JNK特异性抑制剂SP600125,p38特异性抑制剂SB203580,及ERK特异性抑制剂PD98059给予同期干预,检测干预效果。结果随着机械牵张应力的增大,肺泡巨噬细胞MIP-2 mRNA和其蛋白的表达递增(均P<0.05)。给予SP600125干预组大鼠肺泡巨噬细胞MIP-2 mRNA和蛋白表达较机械牵张处理组明显降低。SB203580干预组及PD98059干预组的肺泡巨噬细胞MIP-2 mRNA和蛋白水平较对照组明显升高,而与机械牵张处理组相比无明显变化。而IL-6 mRNA及其蛋白水平在上述各组中均无明显变化。结论大鼠巨噬细胞MIP-2的表达与机械牵张应力呈强度依赖性,JNK信号通路在周期性牵张诱导肺泡巨噬细胞表达释放MIP-2过程中起重要作用。Objective To observe the effects of different mechanical stretch on expression of interleukin-6（IL-6）and Mmacrophage inflammatory protein-2（MIP-2）in rat alveolar macrophages（AMs）,and investigate the role of C-JUN N-terminal kinase（JNK） signaling pathway on IL-6 and MIP-2 expression in AMs which were induced by mechanical stretch.Methods The AMs of rats were get by bronchoalveolar lavage and were cultured in mechanical stretch condition to make stretch model of AMs in vitro.The expression of IL-6 and MIP-2 were determined by RT-PCR and Western blot.For further study,these AMs were interfered by JNK inhibitor SP600125,p38 inhibitor SB203580 and ERK inhibitor PD98059 respectively,and the effects were detected.Results The expression of mRNA and protein of MIP-2 in AMs was up-regulated with increasing stretching force（both P0.05）.The expression of mRNA and protein of MIP-2 in AMs was down-regulated with SP600125,compared with the mechanical stretch group.But expression of MIP-2 mRNA and protein in AMs with PD98059 and SB203580,which had no statistic difference compared with mechanical stretch group,was significant up-regulated compared with the control group.There was no significant difference in IL-6 levels between above groups.Conclusions Mechanical stretch up-regulates the expression of MIP-2 in rat AMs in a intensity-dependent manner.JNK signaling pathway could affect the expression of MIP-2 in alveolar macrophages under mechanical stretch.

关 键 词：C-JUN氨基末端激酶 机械牵张 肺泡巨噬细胞 巨噬细胞炎症蛋白-2 白介素-6 

分 类 号：R322.3[医药卫生—人体解剖和组织胚胎学]