123: High-mobility group box 1 (HMGB1) release in response to hypoxia involves TLR4-dependent production of reactive oxygen species

Abstract

Introduction: HMGB1 is a nuclear factor released extracellularly as a late mediator of lethality in sepsis and as an early mediator of inflammation following acute tissue injury. The mechanisms accounting for HMGB1 release are unknown. We have previously shown that hypoxia in vitro and ischemia-reperfusion (I/R) in vivo result in the upregulation of HMGB1 in hepatocytes. In addition, HMGB1-mediated hepatic injury after I/R is TLR4-dependent. Thus, we hypothesized that the release of HMGB1 due to oxidative stress may be associated with TLR4-dependent production of reactive oxygen species (ROS).