737 The role of bisphenol A in atopic dermatitis

Atopic dermatitis (AD) is characterized by the interaction between immunological, genetic and environmental factors. We hypothesized that daily exposure to noxious molecules such as Bisphenol A (BPA) triggers the disease by promoting the transition from healthy to non-lesional AD. Mice topically exposed to BPA showed increased transepidermal waterloss, indicating epidermal barrier impairment. In line with this, ultrastructural analysis of the epidermis revealed abnormal lamellar body cargo and secretion system, as well as altered corneodesmosomes, leading to a decreased cohesion of the stratum corneum. Furthermore, topical BPA treatment led to AD-like symptoms including atopic skin and systemic effects. Moreover, topical BPA decreased the activity of the complex I of the mitochondrial respiratory chain, suggesting altered mitochondrial function. Accordingly, amounts of lipid peroxides were increased, demonstrating oxidative stress. Moreover, amounts of CYP3A and UGT1A1 were enhanced, illustrating xenobiotic metabolism activation. Because pregnane X receptor (PXR) is a master regulator of xenobiotic metabolism, especially CYP3A, we topically treated PXR-/- mice with BPA. BPA-treated PXR-/- mice did not exhibit upregulation of pro-inflammatory mediators such as Il13, TSLP, Il1a, Il1b and CCl17 in the epidermis, neither mast cell infiltration in the dermis, in contrast to BPA-treated wild type mice, suggesting that AD-like symptoms induced by topical BPA are, at least partly, mediated via PXR. Interestingly, LC-MS analysis of BPA in serum and in d-squames collected from AD patients and healthy donors showed a trend increase of BPA levels in the serum of AD patients, as opposed to d-squames. This might owe to a greater penetration of BPA in AD patients through damaged epidermal barrier. Thus, chronic skin exposure to BPA might promote the transition from healthy to AD skin and have implications in the atopic march.