Melatonin Regulates Arylhydrocarbon Receptor Mediated UVR-Induced Processes Related to Inflammation, Skin Aging and...

UV radiation (UVR), a known skin-stressor causing inflammation, aging and carcinogenesis, activates the arylhydrocarbon receptor (AhR) and downstream molecules which are crucially involved in photo-induced skin damage. In this study, the potent UV protector melatonin was investigated regarding UVR-mediated activation of AhR and downstream molecules including tumor suppressor p27, DNA double-strand break marker pH2AX, cyclooxygenase-2 (COX-2), mitogen-activated protein kinase-14 (MAPK14)/p38α, matrix metalloproteinase-2 (MMP2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP1). They were studied in ex vivo human full-thickness skin irradiated with UVA/B light (0, 300 mJ/cm²) 0 h and 24 h post UV exposure, comparing skin pre-incubated with or without melatonin. Protein expression was analysed by immunofluorescence staining, gene expression by real-time qPCR. UV exposure significantly up-regulated AhR (p < 0.0001), p27 (p < 0.001) and pH2AX (p < 0.0001) protein expression 0 h and 24 h post-irradiation which was significantly counteracted by melatonin (10^-3 M) at both time points. Further, melatonin significantly reduced gene expression of AhR by 21.2% (p < 0.01), p27 by 24.8% (p < 0.01), COX-2 by 42.9% (p < 0.001), MAPK14 by 6.6% (p < 0.05) and MMP2 by 8.2% (p < 0.05), and caused a 10.2% (n.s.) TIMP1 reduction tendency 24 h post-irradiation. Thus, melatonin prevented UV-dependent expression of AhR and downstream regulators of AhR-mediated processes possibly related to inflammation, cellular aging and carcinogenesis on protein and gene level in UV-irradiated skin.