皮膚においてNADPH Oxidase(Nox)が産生する過酸化水素(H2O2)は, AQP3あるいは9を介して細胞内に取り込まれることで, 炎症形成と疾患に関与するという仮説を検証した。紫外線B(UVB)照射による皮膚炎症には表皮細胞に発現するNox1が関与していた。表皮細胞では, UVB照射により誘発されるH2O2の産生がNox1欠損によって減少しており, これに伴いp38/MAPK細胞シグナルの活性化の抑制と, 炎症性サイトカイン産生が抑制された。表皮細胞で産生された高濃度のH2O2は, AQP3を介して細胞外へ分泌されている可能性が示され, また皮膚でおこる炎症反応惹起に関与していることも示された。
Members of NADPH oxidase (Nox) enzyme family are important sources of reactive oxygen species (ROS) and are known to be involved in several physiological functions in response to various stimuli including UV irradiation. UVB-induced ROS have been associated with inflammation, cytotoxicity, cell death, or DNA damage in human keratinocytes. However, the source and the role of UVB-induced ROS remain undefined. We found that Nox1 was involved in UVB-induced p38/MAPK activation, cytokine production, and cytotoxicity via ROS generation in keratinocytes. In vivo assay using wild-type mice, the intradermal injection of lysates from UVB-irradiated control cells, but not from UVB-irradiated Nox1 knockdown cells, induced inflammatory swelling and IL-6 production in the skin of ears. These data suggest that Nox1-mediated ROS production is required for UVB-induced cytotoxicity and inflammation through p38 activation and inflammatory cytokine production, such as IL-6.
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