The role of Nox in the pathogenesis of Atopic Dermatitis

为了确定NADPH氧化酶（NOX）在特应性皮炎（AD）中的作用，我采用屋尘螨（HDM）诱导的AD模型，建立NC/Nga小鼠模型。NC/Nga小鼠分别给予或不给予HDM （Dermatophagoides farinae）。在治疗结束时，hdm处理小鼠出现ad样皮肤病变，与对照组相比，出现红斑、擦伤、脱屑、经皮失水和抓伤行为增加。在这种情况下，NOX1在小鼠角质形成细胞中表达，而NOX2在AD皮肤病变中表达增加（HDM组）。进一步，我使用微阵列数据检测了与正常情况相比，AD患者皮肤中NOX1的表达。我发现，与正常皮肤相比，AD中NOX1的表达增加，而NOX2在这些情况下相似。在AD人皮肤中进一步检查发现，NOX1与Th2基因特征呈正相关（r=0.63）， Th2基因特征包括在特应性CD4 t淋巴细胞应答中代表共同表达网络的基因，如IL-5、IL-13；NOX1与表皮生长因子受体信号通路（Epidermal_growth_factor_receptor_signaling_pathway）之间，r=0.78，由表皮生长因子受体与其生理配体之一（如表皮生长因子和TNF α）结合而产生的一系列分子信号组成。这些数据提示NOX1可能在AD的皮肤炎症状况中起作用。总体而言，数据显示NOX1在角化细胞中表达，并且在AD状态下其表达增加，提示NOX1在AD的发展中起重要作用。

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.