Health Hazards and Environmental Contaminant
Health hazards posed by environmental contaminants have been brought to the public’s attention and the results of numerous studies have been published. The skin functions as an immune organ against outside chemicals and pathogens. Several studies have been conducted on carcinogenesis by environmental contaminants; however, little is known about the mechanism of inflammatory reactions to environmental contaminants in the skin. Benzo(a)pyrene (BaP) is an environmental contaminant found in tabacco smoke and one of polycyclic aromatic hydrocarbons (PAHs). Studies on the carcinogenic potential of PAHs have revealed that they are metabolized through aryl hydrocarbon receptor (AhR) signaling pathways in internal organs such as the liver, lung, and colon. However, there are few studies on the metabolism and biology of PAHs in the skin.
In general, themetabolismof PAHs via AhR signaling pathways occurs as follows : (1) Upon cellular entry, PAHs interact with AhR located in the cytoplasm. (2) The PAHs-AhR complex subsequently translocates to the nucleus and forms the heterodimer PAHs/AhR/AhR nuclear translocator (ARNT) in the nucleus. (3) This PAHs/AhR/ARNT complex binds to specific xenobiotic responsive elements (XREs) to synthesize cytochrome P450 enzymes family including subfamily A, polypeptide 1 (CYP1A1). CYP1A1, also known as aryl hydrocarbon hydroxylase, is involved in the metabolization and activation of PAHs to produce reactive oxygen species (ROS). The main cause of carcinogenesis induced by PAHs is oxidative DNA damage exposed to ROS. Furthermore, ROS plays a pivotal role in the intracellular signals and is capable of regulating the expression of proinflammatory cyto/ chemokines.
Considering that BaP is present in tabacco smoke and in the surrounding environment, and that smoking is an aggravating factor in inflammatory skin diseases such as psoriasis, acne, and palmoplantar pustulosis, which are associated with neutrophil infiltration, we hypothesized that BaP might be capable of inducing interleukin (IL)-8 (a potent neutrophil chemoattractant) and other proinflammatory cyto/chemokines from normal human epidermal keratinocytes (NHEKs). The aim of the present study was to clarify whether or not BaP was able to activate AhR signaling pathways in NHEKs leading to ROS and proinflammatory cyto/chemokines production, which, to our knowledge, was previously unreported