In the past decades, the incidence of atopic dermatits (AD) has been increasing in adult population, raising the question of potential environmental triggers. We hypothesized that pollution might be a contributing factor. Bisphenol A (BPA) is an endocrine disruptor with unkown pathophysiological consequences of its repeated skin exposure. We aimed to decipher the effects of topical application of BPA onto human epidermal equivalents (HEEs) generated with keratinocytes isolated from healthy skin biopsies. In parallel, we generated HEEs made with keratinocytes isolated from AD patients’ skin biopsies for comparison with BPA-treated HEEs. Results showed increased mRNA level of pro-inflammatory mediators including IL-1a, IL1b, IL-6, IL-8 and CCL17 both in AD and BPA-treated HEEs. Furthermore, SOD2, SOD1 and VDAC were increased, indicating cellular oxidative stress. Indeed, increased cytochrome P450 (CYP) activity produces ROS in excessive amounts. In line with this, CYP1A1, CYP3A4, UGT1A1, and PXR were upregulated. Effects of BPA might be mediated via PXR signaling because rifampicin-treated HEEs exhibit similar features than those treated with BPA. Moreover, reduced corneodesmosin and biotin-diffusion assay showed impaired tight junctions, suggesting abnormal epidermal barrier formation. To confirm these results in vivo, healthy mice were topically treated with BPA. Results show increased TEWL, indicating epidermal barrier impairment. In line with this, ear and epidermal thickness were increased, indicating skin edema and acanthosis. Moreover, BPA increased skin and systemic Th2-dominant inflammation, including increased dermal infiltration with mast cells. In conclusion, repeated skin exposure with BPA provokes epidermal barrier defect and elicits inflammation resembling AD. This might result from the activation of the xenobiotic metabolism, via the production of excessive oxidative stress.

ESDR205 - Topical application of Bisphenol A leads to atopic dermatitis-like features

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.