Role of Benzo (a) Pyrene in exacerbating the skin inflammation in Psoriatic mouse model

Abstract

Emerging evidence suggests that environmental chemicals, mainly the organic pollutants like polycyclic hydrocarbons (PAHs), could contribute to the pathophysiology of several chronic inflammatory skin diseases like atopic dermatitis and psoriasis. Benzo[a]pyrene (BaP), the main source of atmospheric PAH, is generated mainly from cigarette smoke, wood-burning and automobile exhaust. Several reports suggest that the inflammatory effects exerted by BaP could be mediated via the aryl hydrocarbon receptor (AhR) signaling pathway. AhR ligands exert the antioxidative pathway triggered by injury and inflammation, and could activate the nuclear factor-erythroid 2-related factor-2 (NRF2). Pathology of Psoriasis includes acanthosis, hyperkeratosis, and parakeratosis of the epidermis, invasion of neutrophils into the epidermis as well as an inflammatory response. BaP exposure could exacerbate the inflammatory pathology of psoriasis; however, comprehensive studies to assess this and decipher the molecular mechanisms involved, remain elusive. In the present study, we evaluated the effect of BaP on mouse skin psoriasis. For generating psoriasis, the dorsal skin of C57BL/6 male and female mice was shaved and exposed to 62.5mg of 5% imiquimod (IMQ) cream once daily for five days. To study the effect of BaP in the exacerbation of IMQ- induced psoriasis, mice were exposed to 64µg BaP in 50µl acetone for five days before IMQ application [BaP+IMQ] or for five days together with the IMQ [(BaP+IMQ)] application. Histopathological analysis showed that BaP exposure together with IMQ exacerbated IMQ-induced psoriatic inflammatory lesions including the skin bi-fold thickness, epidermal and dermal thickness, acanthosis, hyperkeratosis, dermal fibrosis and neutrophil infiltration. Our ongoing molecular studies show that the exposure of BaP in IMQ-induced psoriatic mice elevated the expression of inflammatory markers like COX-2, MMP9, myeloperoxidase (maker of neutrophil infiltration) and NRF2. Increased expression of these markers suggests that BaP could activate inflammatory pathways and further elevate the skin inflammation in IMQ induced psoriasis. Further mechanistic studies are underway to evaluate the pathways involved in BaP-induced exacerbation of psoriasis.