title: Hypoxia inducible factor-1α contributes to UV radiation-induced inflammation, epidermal hyperplasia and immunosuppression in mice.
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.
authors: Faculty of Veterinary Science, University of Sydney, Sydney, NSW, Australia.
authors: Jun-Lae
authors: JL
authors: Cho
authors: Munif
authors: M
authors: Allanson
authors: Vivienne E
authors: VE
authors: Reeve
mesh_terms: D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004487:Edema / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects; D006965:Hyperplasia / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D007108:Immune Tolerance / Q000528:radiation effects*; D007191:Indazoles / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; D015850:Interleukin-6; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole