Differential Regulation of Free Radicals (Reactive Oxygen and Nitrogen Species) by Contact Allergens and Irritants in Human Keratinocyte Cell Line

Abstract

Immune responses to chemicals resulting in sensitization and the appearance of allergic responses following subsequent exposures are dependent upon activation of T lymphocytes. On the contrary, irritant responses are independent of immune response. The aim of this project was to identify the differential signaling cascade operated in allergic and irritant contact dermatitis. Recently, we have shown that keratinocyte cell line A431 can function as an antigen presenting cell (APC) and hence can be used as a model to differentiate between an allergen and irritant molecule. Allergen- and irritant-induced regulation of reactive oxygen species (ROS) and nitric oxide (NO) has been explored. Irritants induce release of ROS even at noncytotoxic concentration. ROS generation by allergens was not detected at nontoxic concentration but as the concentration was increased to a toxic dose there was a drastic increase in the ROS level compared to the untreated cells. Hence, the regulation of ROS is not significant in allergic responses but important in irritant responses. The major difference exists in the fact that the source of ROS for irritants is mitochondria, while that of allergens is mostly cytosolic. Antioxidant-induced protection from irritant-induced cell death has also been demonstrated. NO level was found to increase by allergens and irritants in a concentration-dependent manner. Hence, the regulation of ROS and NO can be used as important mediators in contact allergic and irritant dermatitis.