Role of hypoxia inducible factor-1 in keratinocyte inflammatory response and neutrophil recruitment
1 Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
2 School of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark
3 Rady Children’s Hospital, San Diego, California, USA
4 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
5 University of Queensland, Brisbane, QLD, Australia
Journal of Inflammation 2013, 10:28 doi:10.1186/1476-9255-10-28Published: 10 August 2013
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.
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.
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.