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.


RESULTS
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.
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA. anhollands@ucsd.edu.
Emma
E
Leire
Josh
J
Olson
Hart
H
Isaacs
Victor
V
Nizet
Andrew
A
Hollands