Hypoxia-induced release of HMGB1 in alveolar macrophages and its potential mechanism

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.