Role of hypoxia inducible factor-1 in keratinocyte inflammatory response and neutrophil recruitment

BACKGROUND: Hypoxia inducible factor-1 (HIF-1) is a major regulator of the cellular adaption to low oxygen stress and the innate immune function of myeloid cells. Treatment with the novel HIF-1 stabilizing drug AKB-4924 has been shown to enhance the bactericidal activity of keratinocytes as well as phagocytic cells. In this study, we sought to investigate the effect of pharmacological boosting of HIF-1 with AKB-4924 in keratinocytes and their contribution to the innate immune response. FINDINGS: Treatment with the novel HIF-1 stabilizing drug AKB-4924 can increase keratinocyte production of pro-inflammatory cytokines in vitro and enhance neutrophil recruitment in vivo. CONCLUSIONS: HIF plays an important role in cytokine production by keratinocytes and in neutrophil recruitment to the skin. The HIF-boosting drug AKB-4924 has the potential to enhance the immune response even in the complex environment of bacterial skin infections.