Redox regulation of cutaneous AMPs by ozone in tensioned skin models

Ozone-induced inflammation has been linked to the development of skin ailments including atopic dermatitis, acne vulgaris, eczema and psoriasis, mainly through a redox-inflammatory pathway. While ozone cannot penetrate the cutaneous layers, it is able to damage the skin through oxinflammatory reactions in the epidermis that lead to the generation of lipid-peroxides, aldehydes, and H2O2. When the production of these bioactive oxidative molecules overwhelms the cutaneous redox defenses, cutaneous damage incurs. Antimicrobial peptides (AMPs) are effector molecules that regulate a variety of cutaneous immune responses. Increased AMPs levels have also been detected in active lesions of inflammatory skin diseases. Our previous research has shown that exposure to either ozone induced the expression of cutaneous AMPs (LL-37, beta-defensin 2, and beta-defensin 3) levels in ex vivo skin explants, corroborating the hypothesis that ozone exposure might worsen inflammatory skin conditions via AMPs de-regulation. In the present work, to further assess the cutaneous AMPs responses in a more physiological setting, skin models cultured under physiological tension (TenBio) were expose to ozone. As a proof of concept, cutaneous models were pre-treated with a variety of redox inhibitors (catalase, deferoxamine (DFO) and VAS2870 (VAS)) before ozone exposure to better understand the involvement of a redox signaling. Our data demonstrates that even in the most realistic cutaneous ex vivo model, ozone induces LL-37, hBD2, and hBD3 protein levels through a redox mechanism. This study lays the basis to uncover the mechanisms of ozone dysregulation of cutaneous AMPs, a fundamental step to understanding the development/worsening of pollution-linked inflammatory skin conditions.