ynurenine inhibits melanogenesis in human melanocyte-keratinocyte co-cultures and in a reconstructed 3D skin mode

Author(s)

Ferreira Branquinho, Maryana Stephany ^[1] ; Barros Silva, Maysa Braga ^[1] ; Castilho, Gabriela Ansanelo ^[1] ; Cavalcante, Jacqueline ^[1] ; de Moraes Barros, Silvia Berlanga ^[2] ; Clara, Renan Orsati ^[1] ; Maria-Engler, Silvya Stuchi ^[2] ; Campa, Ana ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin Chem & Toxicol, Ave Prof Lineu Prestes 580, Block 17, Room 110, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin Chem & Toxicol, Skin Lab, Sao Paulo - Brazil

• Document type: Journal article
• Source: EXPERIMENTAL DERMATOLOGY; v. 31, n. 3 NOV 2021.
• Web of Science Citations: 0

Abstract

Kynurenine (KYN), the most abundant metabolite of tryptophan, is classically associated with immune tolerance and tumor immune escape. In the last years, KYN is in the spotlight in other biological processes. Here, we showed that KYN inhibited tyrosinase expression and melanin content in primary human melanocyte and keratinocyte co-cultures. Furthermore, KYN decreased melanosome content in a 3D human skin reconstruction model. In these experiments, we used tyrosine + NH4Cl to induce pigmentation. We compared the inhibitory effect of KYN on melanogenesis with the already known inhibitory effect promoted by IFN-gamma. Since increased KYN production depends on the IFN-gamma-inducible enzyme indoleamine-2,3-dioxygenase (IDO), we propose that part of the effect of IFN-gamma on melanogenesis involves KYN production. From that, we tested if, during melanogenesis, changes in tryptophan metabolism would occur. For this purpose, we measured tryptophan, KYN and downstream products along with pigmentation. There were no significant changes in Trp metabolism, except for the high consumption of kynurenic acid. Our data identify the skin as a potential target for the action of KYN relevant for skin physiology and pigmentation. The results are discussed concerning the high production of KYN in skin inflammatory disorders and cancer. (AU)

• FAPESP's process: 19/14527-7 - Skin bioprinting as a plataform for alternative tests of efficacy and safety
• Grantee: Silvya Stuchi Maria-Engler
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/04926-6 - Melanoma and chemoresistance: in vitro and in silico models to exploit therapeutic targets
• Grantee: Silvya Stuchi Maria-Engler
• Support Opportunities: Research Projects - Thematic Grants