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Hypoxia inducible factor-1α contributes to UV radiation-induced inflammation, epidermal hyperplasia and immunosuppression in mice

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Abstract

Hypoxia inducible factor-1α (HIF-1α), a ubiquitous inducible oxygen-sensing transcription factor, promotes cell survival under hypoxic conditions, including the early pre-angiogenic period of tumorigenesis, and is known to contribute to many malignancies. However HIF-1α can also be activated by inflammatory mediators, and can activate inflammation-modulating proteins itself, including heme oxygenase-1 (HO-1) and the cytokine IL-6. Recently HIF-1α was reported to be induced by UVB (290–320 nm) radiation in cultured human keratinocytes, acting as a stress protein associated with the release of reactive oxygen species. In this in vivo murine study we demonstrate that HIF-1α protein is an early responder to UV radiation in the skin, and its activation can be attenuated by treating mice with its post-translational inhibitor, YC-1. Treatment with YC-1 following UV-irradiation of mice has revealed the involvement of HIF-1α in UV-induced inflammation, IL-6 production, and epidermal hyperplasia. In addition, upregulated cutaneous HIF-1α was found to be an important factor in the UV-suppression of T cell-mediated immunity, measured by contact hypersensitivity (CHS). The mechanism remains unclear, however it did not appear to involve the immunosuppressive cutaneous photoproduct cis-urocanic acid, but HIF-1α induction was inhibited by irradiation with photoimmune protective UVA (320–400 nm), implicating a negative correlation between the two stress proteins, HIF-1α and the photoimmune protective UVA responder HO-1.

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  1. Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia

    Jun-Lae Cho, Munif Allanson & Vivienne E. Reeve

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Cho, JL., Allanson, M. & Reeve, V.E. Hypoxia inducible factor-1α contributes to UV radiation-induced inflammation, epidermal hyperplasia and immunosuppression in mice. Photochem Photobiol Sci 11, 309–317 (2012). https://doi.org/10.1039/c1pp05265a

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