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J Invest Dermatol. 2008 Aug;128(8):1964-8. doi: 10.1038/jid.2008.27. Epub 2008 Mar 6.

Critical role of HIF-1alpha in keratinocyte defense against bacterial infection.

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  • 1Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0377, USA.


Skin, the first barrier against invading microorganisms, is hypoxic, even under baseline conditions. The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha, the principal regulator of cellular adaptation to low oxygen, is strongly expressed in skin epithelium. HIF-1alpha is now understood to play a key role in the bactericidal capacity of phagocytic cells such as macrophages and neutrophils. In the skin, keratinocytes provide a direct antibacterial activity through production of antimicrobial peptides, including cathelicidin. Here, we generate mice with a keratinocyte-specific deletion of HIF-1alpha and examine effects on intrinsic skin immunity. Keratinocyte HIF-1alpha is seen to provide protection against necrotic skin lesions produced by the pathogen group A Streptococcus. RNA interference studies reveal that HIF-1alpha regulation of keratinocyte cathelicidin production is critical to their antibacterial function.

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