TNF参与内毒素诱导肥大细胞HMGB1释放

Involvement of TNF in HMGB1 release of lipopolysaccharide-induced mast cells

目的探讨肿瘤坏死因子-α(TNF-α)在内毒素诱导肥大细胞高迁移率族蛋白B1(HMGB1)释放中的作用。方法采用小鼠肥大细胞株P815培养物,观察100μg/L脂多糖(LPS)诱导后培养上清液中HMGB1、TNF-α含量的变化,不同剂量抗TNF-α中和抗体IgG对LPS诱导HMGB1释放的影响,及TNF-α对HMGB1释放的诱导作用。HMGB1含量采用酶联免疫吸附试验检测。结果培养上清液中HMGB1含量随LPS诱导时间而升高,而TNF-α含量于诱导6 h时达到峰值;5、25 mg/L抗TNF-α抗体对LPS诱导HMGB1释放有明显的抑制作用(P<0.05);TNF-α显示具有诱导肥大细胞释放HMGB1的作用,并呈时间、剂量相关性。结论 TNF-α参与内毒素诱导肥大细胞释放HMGB1的过程。

Objective To study the effect of TNF-α in extracellular release of high mobility group box 1（HMGB1） in endotoxin-induced mast cells.Methods The concentrations of HMGB1 and TNF-α in the culture medium were analysed by ELISA,and the effect of anti-TNF-α neutralizing antibody with various concentrations was observed on HMGB1 release,after P815 mast cells were induced with 100 μg/L lipopolysaccharide（LPS）.HMGB1 release was investigated in P815 mast cells induced by mouse TNF-α.Results HMGB1 level in the culture medium time-dependently increased after mast cells were induced with LPS,and TNF-α level tended to peak 6 hours after induction.Anti-TNF-α antibody with 5 mg/L and 25 mg/L significantly inhibited LPS-induced production of HMGB1 by mast cells（P〈0.05）.TNF-α dose-and time-dependently induced extracellular release of HMGB1.Conclusion Endotoxin induces mast cells to release HMGB1 partly through TNF-α-dependent mechanism.