In vivo role of HMGB1 in endotoxemia and bacterial infection (IRC5P.454)

Abstract

Abstract High-mobility group box protein 1 is nuclear protein conserved among almost all eukaryotic cells. HMGB1 is thought to be a danger signal mediator when it is released both actively from activated immune cells and passively from dead cells into extracellular milieu upon pathogen infections or sterile inflammations. Released HMGB1 act as an inflammatory cytokine and promote inflammatory disorders. However, in vivo function of HMGB1 is still elusive since Hmgb1 gene-deficient mice are lethal. In this study, by using Hmgb1 gene conditional knockout mice which we have established recently, we examined the role of HMGB1 in innate immune responses and inflammation in vivo. We successfully generated Hmgb1fl/flLysM-Cre+ mice because it has been reported that HMGB1 is released from myeloid cells. They developed without significant anomaly and HMGB1 is deleted from macrophages. Interestingly, we observed that, in LPS induced endotoxin shock model, Hmgb1fl/flLysM-Cre+ mice became more sensitive while plasma HMGB1 level of Hmgb1fl/flLysM-Cre+ mice is comparable with wild-type control. These mice also became more susceptible to bacterial infection. In this poster session, we would like to discuss these and recent data further.