The role of Nox in the pathogenesis of Atopic Dermatitis

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To determine the role of NADPH oxidase (NOX) in atopic dermatitis (AD), I use house dust mite (HDM)-induced AD model in NC/Nga mouse, which have been reported as AD-mouse model previously. NC/Nga mouse were treated with or without HDM (Dermatophagoides farinae). At the end of the treatment, HDM-treated mouse showed AD-like skin lesion with erythema, excoriation, scaling, increased of transepidermal water loss and scratching behavior compare to control mouse. In this condition, NOX1, but not NOX2, is expressed in mouse keratinocytes and increased in AD skin lesion (HDM group).Further I examined the expression of NOX1 in human skin of AD compare to normal condition using microarray data. I found an increased of NOX1 expression in AD compare to normal human skin, while NOX2 is similar between those conditions. Further examinations in AD human skin revealed a positive correlation (r=0.63) between NOX1 and the Th2 gene signatures, which consists of genes representing a co-expression network in atopic CD4 T-lymphocytes responses e.g. IL-5, IL-13; also between NOX1 and Epidermal_growth_factor_receptor_signaling_pathway, r=0.78, consists of series of molecular signals generated as a consequence of an epidermal growth factor receptor binding to one of its physiological ligands, e.g. epidermal growth factor and TNF alpha. These data suggest that NOX1 may have a role in the skin inflammation condition of AD.Overall, the data show that NOX1 is expressed in keratinocytes and its expression is increased in AD condition, suggesting an important role of NOX1 in the development of AD.