高迁移率族蛋白1促进巨噬细胞表达IL-18及其受体

目的:探讨高迁移率族蛋白1(HMGB1)能否激活巨噬细胞表达IL-18及其受体。方法:HMGB1与小鼠腹腔巨噬细胞共孵育后,采用实时RT-PCR、ELISA和流式细胞术分别检测IL-18的基因表达和蛋白含量以及IL-18受体(IL-18R)表达水平。Toll样受体(Toll-like receptor,TLR)2激动剂Pam3Cys(1μg/ml)和TLR4激动剂脂多糖(LPS,100 ng/ml)设为平行对照。结果:100 ng/ml HMGB1刺激巨噬细胞2 h,IL-18 mRNA的表达明显增加;HMGB1刺激24 h后IL-18蛋白的产生明显增加,并且轻度上调细胞表面IL-18R的表达。TLR2激动剂Pam3Cys和TLR4激动剂LPS也能促进IL-18的基因表达和蛋白产生以及上调IL-18R的表达。结论:HMGB1可以直接激活巨噬细胞表达IL-18及其受体,提示HMGB1在炎症反应中可能通过IL-18加强致炎作用。

High mobility group box chromosomal protein 1 promotes IL-18 production and IL-18 receptor expression in macrophages

Objective:To investigate whether high mobility group box chromosomal protein 1(HMGB1)can activate macrophages to secrete IL-18.Methods:Mouse peritoneal maerophages were cultured with HMGB1 for indicated period,then the mRNA and protein expression of IL-18 and IL-18 receptors were examined by real-time PCR,ELISA,and flow cytometric analysis.Toll-like receptor(TLR)2 and 4 agonists(1/μg/ml Pam3Cys or 100 ng/ml LPS)were used as parallel controls.Results:Two hours after culture with HMGB1(100 ng/ml),IL-18 mRNA expression was greatly increased.The expression of IL-18 protein was also greatly increased 24 h after culture with HMGB1,and the expression of IL-18R was slightly upregulated.Pam3Cys(1 μg/ml)and LPS(100 ng/ml)could promote the expression of IL-18 at both mRNA and protein levels in the macrophages,and could up-regulate IL-18 receptors.Conclusion:HMGB1 can directly activate macrophages to secrete IL-18 and to express IL-18 receptor,suggesting that IL-18 may mediate the proinflammatory activity of HMGB1.