Aryl Hydrocarbon Receptor as a Therapeutical Target of Environmentally Induced Skin Conditions

Abstract

COX-2 -Cyclooxygenase 2 c-Src -Proto-oncogene tyrosine-protein kinase c-Src CYP1A1 -Cytochrome P450 1A1 CYP450 -Cytochrome P450 DCT -Dopachrome tautomerase DEJ -Dermal epidermal junction ECM -Extracellular matrix elements EGC -Epigallocatechin EGCG -Epigallocatechin gallate EGFR -Epidermal growth factor receptor

Combined exposure to UV and PM affect skin oxinflammatory responses and it is prevented by antioxidant mix topical application: Evidences from clinical study

“…AhR mediates cellular responses to endogenous and exogenous ligands and, in the skin, its activation by exposome factors including polycyclic aromatic hydrocarbons (PAHs) from diesel vehicles, O 3 and UV light have been involved in cutaneous pathological conditions 25,34,59,60 . Moreover AhR is also involved in the modulation of many cutaneous processes such as keratinocyte proliferation, differentiation, skin immunity, epidermal melanogenesis and skin aging, by modulating the activation of MMPs and thus ECM components levels 61,62 …”

“…25 The pre-treatment of the skin with CF Mix, decreased AhR expression by 22% in PM + UV exposed tissues (Figure 3A). Activation of AhR signaling by toxic environmental contaminants has been shown to promote aberrant immune cascades by modulating the expression of proinflammatory mediators including cytokines and the enzyme cyclooxygenases-2 (COX-2), involved in the synthesis of various prostanoids, 34 as well as the activation of the inflammatory pathways inflammasomes. 35 Our results show that human skin exposed to PM + UV displayed increased levels of COX2 compared to unexposed tissues, whereas a significant reduction (29.4%) in the proinflammatory enzyme levels was observed in exposed human skin pretreated with CF Mix (Figure 3B).…”

“…58 AhR mediates cellular responses to endogenous and exogenous ligands and, in the skin, its activation by exposome factors including polycyclic aromatic hydrocarbons (PAHs) from diesel vehicles, O 3 and UV light have been involved in cutaneous pathological conditions. 25,34,59,60 Moreover AhR is also involved in the modulation of many cutaneous processes such as keratinocyte proliferation, differentiation, skin immunity, epidermal melanogenesis and skin aging, by modulating the activation of MMPs and thus ECM components levels. 61,62 Therefore, it was not surprising that AhR expression levels were upregulated in PM + UV skin explants (Figure 3A), suggesting the possible involvement of this receptor in the activation of oxidative/ inflammatory responses of the skin, and its contribution in the skin involved in the propagation of the skin damage in many inflammatory cutaneous conditions.…”

The Effects of Environmental Pollutants and Exposures on Hair Follicle Pathophysiology

“…PAHs are known ligands of the aryl hydrocarbon receptor. In the skin, this receptor plays a critical role in epidermal differentiation and barrier function and has been a pharmaceutical target for treatment of psoriasis and atopic dermatitis [40][41][42][43]. PAHs have been implicated in extrinsic skin aging, pigmentary disruption, and dysbiosis [44][45][46][47].…”