TOLL样受体信号转导通路在内质网应激致炎症反应中的作用

Role of TOLL-like receptor signal transduction pathway in inflammatory reaction induced by endoplasmic reticulum stress

目的探讨TOLL样受体信号转导通路在衣霉素(TM)致人肝癌细胞系HpeG2和人正常肝细胞系L02内质网应激及炎症反应过程中的作用。方法利用实时荧光定量PCR检测衣霉素作用后HepG2和L02细胞中细胞因子IRAK1、TAK1和NF-κB的基因表达水平,利用Western blot检测相应细胞因子的表达水平。结果两种细胞系经TM刺激后,内质网应激标志物GRP78蛋白表达增高;炎症反应标志因子NF-κB在基因水平和蛋白水平表达均呈现增高趋势;TOLL样受体信号转导通路中关键细胞因子IRAK1、TAK1在基因水平和蛋白水平表达呈现增高趋势,差异均具有统计学意义(P均<0.05)。结论 TM刺激HepG2和L02细胞系之后,可诱导出现内质网应激状态并引起细胞内的炎症反应;在内质网应激致炎症反应过程中伴TOLL样受体信号转导通路的激活,TOLL样受体信号转导通路对其发生、发展可能具有一定的调节作用。

Objective To investigate the role of Toll-like receptor signal transduction pathway on the process of endoplasmic reticulum stress and inflammatory reaction induced by tunicamycin （TM）. Methods The transcription levels of IRAK1, TAK1 and NF-KB genes in HepG2 and L02 cells treated by TM were detected by real-time reverse transcription PCR, and the expression level of protein related cytokines was detected by Western blot. Results The levels of GRP78 （marker of endoplasmic reticulum stress） in HepG2 cells and L02 cells significantly increased after treated by TM. The gene transcription and protein expression level of NF-~B （marker of inflammatory response） were both significantly increased in accordance with the concentration and action time compared with those untreated by TM. In Toll-like receptor signal transduction pathway, the expression of key cytokines like IRAK1 and TAK1 showed an increasing trend at gene and protein levels, all with significant differences （all P 〈 0.05）. Conclusions After the stimulation of TM, endoplasmic reticulum stress and inflammatory reaction were induced in HepG2 and L02 cell lines. In the endoplasmic reticulum stress induced activation inflammatory reaction associated with Toll-like receptor signaling pathway, Toll-like receptor signal transduction pathway in the occurrence and development may have a regulatory role.