重组高迁移率族蛋白B1对肺上皮细胞细胞因子释放的影响及其机制
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国家自然科学基金(81070074);南京医科大学科技发展基金重点项目(2010NJMUZ59)


Effects of recombinant HMGB1 on the release of proinflammatory cytokines in lung epithelial cells and its mechanism
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    摘要:

    目的:观察重组高迁移率族蛋白B1(high mobility group box 1,HMGB1)对肺上皮细胞致炎细胞因子释放的影响,并初步探讨其机制-方法:采用BEAS-2B人正常肺上皮细胞,观察1-10-100-1 000 μg/L重组HMGB1蛋白对细胞培养上清液中致炎细胞因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)-白介素(interleukin,IL)-1β-IL-6含量的影响,及10 mg/L Toll样受体4(Toll-like receptor 4,TLR4)抗体处理对HMGB1诱导致炎细胞因子释放的抑制作用-TNF-α-IL-1β和IL-6含量均采用酶联免疫吸附试验检测-结果:不同剂量重组HMGB1诱导肺上皮细胞12 h后,培养上清液中TNF-α-IL-1β-IL-6含量均呈HMGB1剂量依赖性升高;100 μg/L HMGB1分别诱导肺上皮细胞3-6-12和24 h后,培养上清液中TNF-α-IL-1β-IL-6含量均呈显著性升高(P < 0.05或P < 0.01),IL-1β-IL-6含量随诱导时间延长而升高,而TNF-α含量于诱导后6 h 达峰值;TLR4抗体处理后TNF-α-IL-1β-IL-6释放均受到部分抑制(P < 0.05或P < 0.01)-结论:HMGB1对肺上皮细胞释放TNF-α-IL-1β和IL-6具有诱导作用,其机制可能与胞膜TLR4有关-

    Abstract:

    Objective:To investigate the effects of high mobility group box 1(high mobility group box1,HMGB1) on the extracellular release of proinflammatory cytokines in lung epithelial cells,and its possible mechanism. Methods:The cytokines levels of tumor necrosis factor-α (TNF-α),interleukin(IL)-1β,IL-6 in the culture supernatants of BEAS-2B human lung epithelial cells was determined by ELISA assay after induction with different concentrations of recombinant HMGB1 protein (1,10,100 and 1000 μg/L). The inhibitory effect of Toll-like receptor 4 (TLR4) antibody (10 mg/L) on the release of these cytokines was observed. Results:Recombinant HMGB1 dose-dependently increased the levels of TNF-α,IL-1β and IL-6 in the culture supernatants of BEAS-2B cells. The levels of IL-1β and IL-6 in the culture supernatants were time-dependently increased,and TNF-α level reached to the peak after 6 h induction of 100 μg/L HMGB1. TLR4 antibody partly inhibited HMGB1-induced release of TNF-α,IL-1β and IL-6 (P < 0.05 or P < 0.01). Conclusion:HMGB1 can induce lung epithelial cells to release TNF-α,IL-1β and IL-6,and TLR4 may be involved in the regulatory mechanism.

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吴国荣,王发龙,陈 文,陈静瑜,刘 洁,王 琼,赵 琪,陈国千.重组高迁移率族蛋白B1对肺上皮细胞细胞因子释放的影响及其机制[J].南京医科大学学报(自然科学版),2012,(5):641-644

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  • 收稿日期:2011-12-15
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