Aquaporin-3-mediated hydrogen peroxide transport is required for NF-?B signalling in keratinocytes and development of psoriasis.

ABSTRACT: 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-?B (NF-?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-?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-? is facilitated by AQP3 and required for NF-?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-? stimulation. Collectively, these data indicate that AQP3-facilitated H2O2 transport is required for NF-?B activation in keratinocytes in the development of psoriasis.

SUBMITTER: Hara-Chikuma M 

PROVIDER: S-EPMC5628617 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature