Uncoupling melanogenesis from proliferation in epidermal melanocytes responding to stimulation with psoriasis-related proinflammatory cytokines

Background: Few studies have addressed the impact of the psoriasis-related proinflammatory cytokines on the proliferation and melanogenesis of melanocytes (MCs) in lesional psoriatic skin. Objective: We investigated the effects of TNF alpha, IL17A, and IL8 on the proliferation and melanin synthesis of MCs.Methods: Skin specimens were biopsied from patients with psoriasis vulgaris at the active stage, or from the tail skin of Dct-LacZ mice with imiquimod (IMQ)-induced psoriasiform dermatitis. Cultured keratino-cytes (KCs), MCs, and human skin explants were used in this study. The numbers of MCs were measured via beta-galactosidase staining, EdU incorporation and HMB45 immunohistochemical staining. The expression of human beta-defensin 3 (hBD3) in KCs was silenced by siRNA, the conditioned medium (CM) from siRNA-transfected KCs was used to treat MCs, then followed by alpha MSH stimulation. The melanogenesis-related genes were examined by using qRT-PCR and western blotting. Results: The increased number of MCs and decreased melanin content were highly relevant to the enhanced expression of IL8 and BD3 both in human psoriatic skin and in IMQ-treated mouse tail skin. IL8 expression in KCs and CXCR2 expression in MCs was significantly increased by IL17A and TNF alpha, the alpha MSH-induced upregulations of microphthalmia-associated transcription factor (MITF) and tyrosinase in MCs were abro-gated by the CM from hBD3-unsilenced KCs, but not from hBD3-silenced KCs.Conclusion: Our results suggest the roles of IL8-CXCR2 activation in promoting MC proliferation and of BD3 upregulation in reducing melanogenesis. These findings have been implicated in the underlying mechanism that active psoriasis prefers hypopigmentation despite chronic inflammation.(c) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Automated summary

This study investigated the effects of psoriasis-related proinflammatory cytokines on the proliferation and melanogenesis of melanocytes. The increased expression of IL8 and BD3 was associated with an increased number of melanocytes and reduced melanin content. IL8-CXCR2 activation promoted melanocyte proliferation, while BD3 upregulation inhibited melanin synthesis, suggesting that active psoriasis tends to prefer hypopigmentation despite chronic inflammation.