期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms8454
关键词
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资金
- Astellas Pharma Inc. in the Creation of Innovation Centers for Advanced Inter disciplinary Research Areas Program
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- U.S. National Institutes of Health [DK35124]
- Grants-in-Aid for Scientific Research [24111001, 24111009] Funding Source: KAKEN
Aquaporin 3 (AQP3), a water/glycerol channel protein, has been found to transport hydrogen peroxide (H2O2). Here, we show that H2O2, imported via AQP3, is involved in nuclear factor-kappa B (NF-kappa B) signalling in keratinocytes and in the pathogenesis of psoriasis. IL-23-mediated induction of psoriasis is reduced in AQP3 knockout mice (AQP3(-/-)), and is accompanied by impaired NF-kappa B activation and intracellular H2O2 accumulation. In primary keratinocyte cultures, cellular import of H2O2 produced by membrane NADPH oxidase 2 (Nox2) in response to TNF-alpha is facilitated by AQP3 and required for NF-kappa B activation by regulation of protein phosphatase 2A. As AQP3 associates with Nox2, we propose that this interplay constitutes H2O2-mediated signalling in response to TNF-alpha stimulation. Collectively, these data indicate that AQP3-facilitated H2O2 transport is required for NF-kappa B activation in keratinocytes in the development of psoriasis.
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