Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte

Abstract

Interferon-γ (IFN-γKey words interferon-γ (IFN-γ); 5-hydroxytryptamine (5-HT); cross-talk; melanogenesis; migration Skin is the largest organ in human body, which plays a role as biologically active barrier to the external environment. It acts not only as a target for neuroendocrine signals but also a source of hormones and neurotransmitters, particularly the epidermis.1) Epidermis and dermis are the two main parts of skin. Epidermal melanocytes, derived from the neural crest, can produce melanin to absorb ultraviolet radiation and provide photoprotection.2) Melanin is synthesized in melanosomes, which are specialized lysosomerelated organelle (LRO) of pigment cells devoting to the biosynthesis, storage and transport of melanin.3) Melanosomes undergo 4 maturation stages, each characterized by unique ultrastructural morphology and melanin content. 4,5) The principal role of the melanocyte is to produce the pigment within melanosomes and to transfer these organelles to upwards of 40 keratinocytes, which are neighboring melanocyte to constitute the 'epidermal melanin unit.' Melanocyte transport melanosomes from the formation site in the cell center to the principal site of transfer at dendritic tips. Accomplishing this feat, melanocyte needs to couple long-range, bidirectional microtubule-dependent transport of melanosomes along the length of dendrites with the capture and local movement of the organelles in actin-rich dendritic tips by the actin-based motor protein myosin Va. 5,6) Studies have shown that there are four possible mechanisms described for melanosome transfer, including the cytophagocytosis model, membrane fusion model, shedding-phagocytosis model and exocytosis-endocytosis model. 6) In addition, multifarious signaling pathways and transcription factors firmly manage melanocyte migration. These proteins and pathways provide and integrate signals to create the proper environment for its normal development and migration. 2)Melanin biosynthesis process is under a complex control mediated by multiple elements through different pathways. A series of pigment cell-specific melanosomal proteins are responsible for melanogenesis, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT). 7-9) Skin cells can produce hormones, neurotransmitters and neuropeptides and corresponding functional receptors, owing to which constitute the cutaneous equivalent of the hypothalamic-pituitary-adrenal (HPA) axis.10,11) It has recently uncovered that cutaneous expression of the biochemical machinery involved in the sequential transformation of L-tryptophan to serotonin and melatonin. 12,13) Serotonin 5-hydroxytryptamine (5-HT) is a neurotransmitter whose actions are mediated via an interaction with receptors, including seven families (5-HT 1-7 receptors) with at least 21 subtypes. Skin cells express mRNA encoding 5-HT receptors, 5-HT 1A, -1B, -2A, -2B, -2C, and -7 receptor.14,15) 5-HT 2A receptor was reported participating in the regulatory processes of 5-HT on melanogenesis.16) Our preli...

Network pharmacological mechanisms of Vernonia anthelmintica (L.) in the treatment of vitiligo: Isorhamnetin induction of melanogenesis via up-regulation of melanin-biosynthetic genes

“…The arachidonic acid metabolism pathway and serotonergic synapses existed in keratinocytes, as well as pigment cells, which excreted regulative factors, such as PGE2, HETE and 5-HT. These regulative factors stimulated the proliferation of melanocytes and enhanced melanogenesis [ 39 , 40 ]. The melanogenic pathway was activated by Isorhamnetin and Kaempferide (Fig.…”

Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures and in a reconstructed 3D skin model

“…An additional aspect of this study is the attempt to elucidate part of the mechanism of the known anti‐melanogenic effect of IFN‐γ. In addition to its well‐defined role in tissue homeostasis and immune/inflammatory responses, IFN‐γ leads to inhibition of TYR synthesis 14–18 . It is still unclear whether these effects result only from biochemical signalling cascades or if they comprise broader modulations, such as inflammatory and immune responses triggered by pigmentation 19 .…”

Papel do metabolismo de triptofano e do interferon-γ na melanogênese

“…O mecanismo de melanogênese e sua interação com o sistema imunológico e suas citocinas mantem a homeostase da pele. Já foi proposto anteriormente que o IFN-γ pode ser um potente inibidor da pigmentação da pele (Natarajan, Vivek T. et al, 2014;Son et al, 2014a;Yang, L. L. et al, 2015;Zhou, Ling, et al, 2016b).…”

“…Vários estudos já abordaram a relação da melanogênese com o metabólito 5-HT (Nordlind et al, 2008;Zhou, Ling, et al, 2016b;Slominski et al, 2017). Este composto tem ação indutora sobre a pigmentação, uma vez que o tratamento com 5-HT resultou no aumento dose dependente da atividade de TYR e da concentração de melanina em melanócitos.…”

“…Este composto tem ação indutora sobre a pigmentação, uma vez que o tratamento com 5-HT resultou no aumento dose dependente da atividade de TYR e da concentração de melanina em melanócitos. Esses resultados foram acompanhados de alterações dos níveis de expressão MITF, TYRP-1 e DCT (Zhou, Ling, et al, 2016b). Além da 5-HT, pesquisadores utilizaram o composto BW723C86, um agonista do receptor 2B de 5-HT, para investigar o papel funcional deste receptor na melanogênese.…”