title: Interferon-γ Attenuates 5-Hydroxytryptamine-Induced Melanogenesis in Primary Melanocyte.
abstract: Interferon-γ (IFN-γ) is an important cytokine which can be secreted by keratinocytes or macrophages induced by UVB irradiation in skin. Mammalian skin cells have the capability to produce and metabolize 5-hydroxytryptamine (5-HT) whose cutaneous effects are mediated by the interactions with 5-HT receptors. Treatment with 5-HT resulted in a dose-dependent increase of tyrosinase (TYR) activity and melanin contents in normal human foreskin-derived epidermal melanocytes (NHEM), while with IFN-γ a decreased effect resulted. These regulatory results were due to changes of the expression levels of microphthalmia-associated transcription factor (MITF) and its downstream TYR, tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT). We proved here that 5-HTR1A/2A participated in the regulation of melanogenesis. IFN-γ could offset the pro-melanogenesis effect of 5-HT in NHEM and the intensity of this neutralization was unanticipated below the baseline level. IFN-γ neutralized the up-regulation effect of 5-HT on MITF and downstream TYR, TRP-1 and DCT. Though functioning as 5-HT1A/2A receptor during the melanogenesis process, IFN-γ played no role in 5-HT1A/2A receptor expressions. Our results also demonstrated that the inhibition of IFN-γ was reversible after its removal. Confusingly, the effect of cross-talk between 5-HT and IFN-γ on NHEM melanogenesis was irreversible. Whether treated with 5-HT for 5 d or 12 d, the pigmentation level neither recovered after displacing the IFN-γ-containing medium. In addition, IFN-γ was able to inhibit the inductive effect of 5-HT on NHEM migration. Taken together, the suppression of IFN-γ on 5-HT-induced melanogenesis further suggests the negative role of IFN-γ in inflammation-associated pigmentary changes.
authors.affiliation: School of Pharmaceutical Science, Jiangnan University.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ling
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Ping
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D052816:Foreskin / Q000166:cytology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C497234:MITF protein, human; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; D044402:Receptor, Serotonin, 5-HT2A; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D007371:Interferon-gamma; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase