Hypoxia-induced release of HMGB1 in alveolar macrophages and its potential mechanism
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摘要:
目的:研究缺氧对肺泡巨噬细胞高迁移率族蛋白B1(high mobility group box1,HMGB1)释放的作用及其信号通路-方法:采用大鼠肺泡巨噬细胞NR8383,观察不同时间缺氧培养对细胞HMGB1 mRNA表达和培养上清液中HMGB1含量的影响,及不同浓度JAK2抑制剂tyrphostin AG 490和STAT1抑制剂氟达拉滨对HMGB1释放的抑制作用-HMGB1含量采用酶联免疫吸附试验检测-结果:培养上清液中HMGB1含量和mRNA表达水平分别于缺氧培养6-12 h后明显升高(P < 0.01),并随缺氧培养时间延长而进一步升高和增强;tyrphostin AG 490和氟达拉滨对缺氧培养肺泡巨噬细胞释放HMGB1有不完全的抑制作用,并呈剂量依赖性-结论:缺氧诱导肺泡巨噬细胞释放HMGB1,JAK/STAT信号通路可能参与其释放过程-
Abstract:
Objective: To study the effect of hypoxia on extracellular release of high mobility group box 1(HMGB1) in hypoxia-induced alveolar macrophages and its potential signaling pathway. Methods: The changes of HMGB1 mRNA expression and HMGB1 concentration in the culture medium were investigated after rat alveolar macrophages (NR8383) were subjected to hypoxia (1% O2) for different hours. The effect of JAK/STAT pathway inhibitors (tyrphostin AG 490 and fludarabine) with various concentrations on the HMGB1 release was observed. HMGB1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). Results: HMGB1 concentration in the culture medium and HMGB1 mRNA expression significantly increased in a time-dependent manner after NR8383 cells were subjected to hypoxia culture. Tyrphostin AG 490 and fludarabine partly inhibited extracellular release of HMGB1 in hypoxia-induced NR8383 cells in a dose-dependent manner. Conclusion: Hypoxia induces alveolar macrophages to release HMGB1,the mechanism may be involved with intracellular JAK/STAT signaling pathway.
