Exposure to Environmental Pollutant Benzo[a]pyrene Exacerbates Skin Inflammation in a Mouse Psoriatic Model

Abstract

A rapid increase in the global prevalence of skin inflammatory diseases like psoriasis cannot be attributed to genetics alone. Environmental factors including major ubiquitous organic pollutants like polycyclic aromatic hydrocarbons (PAHs) could contribute to their pathophysiology. Benzo[a]pyrene (BaP) is one of the PAH that is generated mainly from cigarette smoke, wood‐burning, automobile exhaust etc. The molecular mechanisms that lead to inflammatory skin diseases following exposure to BaP are not well elucidated, though there are suggestions that these responses could be mediated by aryl hydrocarbon receptor (AhR), a xenobiotic sensor. To investigate the effect of BaP exposure on skin inflammation in a mouse psoriatic model, the dorsal skin of naïve C57BL/6 mice was shaved (48h prior to exposure) and exposed to 62.5mg of 5% imiquimod (IMQ) cream once daily for five days. For assessing the initiation or exacerbation of psoriasis from exposure to BaP, mice were exposed 64μg BaP in 50μl acetone for five days before IMQ application [BaP+IMQ] or for five days together with the IMQ [(BaP+IMQ)] application. Following the analysis and scoring of clinical lesions, mice were sacrificed, and skin sections were analyzed for inflammation‐related histopathological and molecular changes. BaP exposure together with IMQ exacerbated IMQ‐induced psoriatic inflammatory lesions including the skin bi‐fold thickness, epidermal and dermal thickness, hyperkeratosis, dermal fibrosis, neutrophil infiltration, neutrophil degeneration and mast cell degranulation. Molecular analysis on the skin samples to further elucidate the effect BaP on IMQ‐induced inflammatory markers such as neutrophil infiltration, macrophages, inflammatory cytokines that could exacerbate psoriasis is being carried out. In other studies, defining the role of AhR in BaP‐induced biological, molecular, and metabolic alterations in mouse skin, concomitant treatment with AhR antagonist CH‐223191 was given before BaP+IMQ treatment. The antagonist treatment before the (BaP+IMQ) treatment abrogated the BaP‐caused increase in epidermal and dermal thickness in psoriatic mice. The effect of the AhR inhibitor on other biological and molecular psoriatic parameters that are exacerbated on exposure to BaP are also being analyzed to decipher the role of AhR in BaP‐induced and/or exacerbation in inflammatory skin diseases like psoriasis.Support or Funding InformationSkaggs Scholars Program Grant, University of Colorado Denver and Start‐up Fund to Neera Tewari‐Singh, Michigan State University