Role of kinin receptors in skin pigmentation

• Published in: European journal of pharmacology Vol. 973; p. 176537
• Main Authors: Ferreira, Juliana de Cassia Pinto, Soley, Bruna Silva, Pawloski, Priscila Lucia, Moreira, Camila Guimarães, Pesquero, João Bosco, Bader, Michael, Calixto, João Batista, Cabrini, Daniela Almeida, Otuki, Michel Fleith
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2024
• Subjects: Animals; Cytokines - metabolism; Humans; Kinin B1 receptor; Kinin B2 receptor; Kinin peptides; Male; Melanin; Melanins - biosynthesis; Melanins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Monobenzone; Reactive Oxygen Species - metabolism; Receptor, Bradykinin B1 - genetics; Receptor, Bradykinin B1 - metabolism; Receptor, Bradykinin B2 - metabolism; Skin - drug effects; Skin - metabolism; Skin - pathology; Skin pigmentation; Skin Pigmentation - drug effects; Vitiligo - metabolism; Vitiligo - pathology; Kinin B1 receptor; Kinin B2 receptor; Skin pigmentation; Monobenzone; Melanin; Kinin peptides
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2024.176537

Previous studies have shown that all kinin system is constitutively expressed in the normal and inflamed skin, with a potential role in both physiological and pathological processes. However, the understanding regarding the involvement of the kinin system in skin pigmentation and pigmentation disorders remains incomplete. In this context, the present study was designed to determine the role of kinins in the Monobenzone (MBZ)-induced vitiligo-like model. Our findings showed that MBZ induces higher local skin depigmentation in kinin receptors knockout mice (KOB1R, KOB2R and KOB1B2R) than in wild type (WT). Remarkably, lower levels of melanin content and reduced ROS generation were detected in KOB1R and KOB2R mice treated with MBZ. In addition, both KOB1R and KOB2R show increased dermal cell infiltrate in vitiligo-like skin, when compared to WT-MBZ. Additionally, lack of B1R was associated with greater skin accumulation of IL-4, IL-6, and IL-17 by MBZ, while KOB1B2R presented lower levels of TNF and IL-1. Of note, the absence of both kinin B1 and B2 receptors demonstrates a protective effect by preventing the increase in polymorphonuclear and mononuclear cell infiltrations, as well as inflammatory cytokine levels induced by MBZ. In addition, in vitro assays confirm that B1R and B2R agonists increase intracellular melanin synthesis, while bradykinin significantly enhanced extracellular melanin levels and proliferation of B16F10 cells. Our findings highlight that the lack of kinin receptors caused more severe depigmentation in the skin, as well as genetic deletion of both B1/B2 receptors seems to be linked with changes in levels of constitutive melanin levels, suggesting the involvement of kinin system in crucial skin pigmentation pathways. [Display omitted] •Kinin receptors play a role in the regulation of skin pigmentation is described.•Absence of both B1 and B2 kinin receptors reduces total melanin content in skin.•Kinin receptors modulate inflammatory responses in vitiligo lesions, controlling infiltration of inflammatory cells and levels of cytokines.•In melanocytes, both kinin receptors have a potential impact on melanin synthesis, and B2 receptors have a correlation with proliferation.