FCP 09 : Transient receptor potential vanilloid (TRPV) inhibition is related to suppression of inflammationassociated hypermelanosis

Background: Pigmented contact dermatitis (PCD) is a skin disorder caused by inflammation-related hyperpigmentation. Patients with PCD often report pruritus and burning sensation on affected areas. These clinical features suggest the possible role of transient receptor potential vanilloid (TRPV) channels in the pathogenesis of PCD. Objectives: We sought to evaluate the expression level of TRPVs in the skin of patients with PCD aiming at identifying crucial receptors related to inflammation-associated melanogenesis. Methods: Immunohistochemical analysis was performed to evaluate cutaneous expression of TRPVs and the mRNA levels of various melanogenesis-related genes were measured using Next-generation sequencing (NGS). Capsaicin, a potent TRPV1 activator, and AMG9810, a selective TRPV1 inhibitor, were used as TRPV regulators in in vitro assays using normal human melanocytes. Results: TRPVs were increased in the epidermal and dermal cells in the lesions of PCD. Pmel, TYRP1 and S100A8 were also increased in the lesions of PCD compared to peri-lesion. qRT-PCR analysis showed that tyrosinase, along with TRPV1 and TRPV3, was up-regulated in patients with PCD. TRPV1 activation promoted melanin synthesis in human melanocytes in vitro, while this effect could be reversed by TRPV1 blockade using AMG9810. A downmodulation of PKC-β II signaling was observed, decreasing the activity of tyrosinase. Conclusion: TRPVs, particularly TRPV1, may play a crucial role in the development, aggravation and chronicit