目的:晚期糖基化终产物受体(RAGE)与其配体结合在炎症及免疫反应中具有重要作用.本研究探讨内质网应激(ERS)在高迁移率族蛋白B1(HMGB1)诱导树突状细胞(DC)表面RAGE上调中的作用及意义.方法:分离正常BALB/c小鼠脾脏DC进行体外培养,给予HMGB1刺激后检测DC表面RAGE表达水平及细胞ERS相关分子表达/活化水平.另外,给予不同剂量ERS特异性诱导剂衣霉素(0.1、1、10μg/ml)刺激24、48、72h,检测DC表面RAGE表达情况.结果:HMGB1刺激诱导DC中ERS相关分子表达/活化水平明显上调(P〈0.05),细胞表面RAGE表达水平也明显上调;衣霉素刺激亦可诱导DC表面RAGE表达增强,且呈一定的时间依赖性,刺激时间越长,RAGE表达水平越高.结论:DC表面RAGE表达水平升高与ERS反应密切相关.
Objective: To clarify the involvement of endoplasmic reticulum stress (ERS) in up-regulation of receptor for advanced glycation endproduets (RAGE) on surface of dendritic cells (IX;) induced by high mobility group box-1 protein (HMGB1). Methods:DCs were isolated from the spleens of male BALB/c mice. Expressions of ERS related molecules were analyzed by Western blot analysis, and the expression of RAGE on surface of DC was determined by flow cytometry after HMGB1 stimulation. The effect of tunicamycin (0. 1,1,10 μg/ml for 24, 48,72 hours) on RAGE expression was also assessed by flow cytometry. Results: HMGB1 induced up-regulation of RAGE expression and significant ERS response in murine splenic DCs. Pharmacological ERS (induced by tunicamycin) resulted in enhanced expression of RAGE on surface of DCs. Conclusions: These results indicate that ERS is crucial for up-regulation of RAGE on surface of DCs.