title: The synthetic melanocortin (CKPV)2 exerts anti-fungal and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization.
abstract: In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH2)2 or (CKPV)2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV)2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV)2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV)2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV)2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP) production was also induced by (CKPV)2 administration in macrophages. These above effects on macrophages by (CKPV)2 were almost reversed by melanocortin receptor-1(MC1R) siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV)2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation.
authors: State Key Laboratory of Natural Medicines, Academic Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China.
authors: Hai-xia
authors: HX
authors: Ji
authors: Yu-lian
authors: YL
authors: Zou
authors: Jing-jing
authors: JJ
authors: Duan
authors: Zhi-rong
authors: ZR
authors: Jia
authors: Xian-jing
authors: XJ
authors: Li
authors: Zhuo
authors: Z
authors: Wang
authors: Li
authors: L
authors: Li
authors: Yong-wen
authors: YW
authors: Li
authors: Gen-yan
authors: GY
authors: Liu
authors: Ming-qing
authors: MQ
authors: Tong
authors: Xiao-yi
authors: XY
authors: Li
authors: Guo-hui
authors: GH
authors: Zhang
authors: Xiang-rong
authors: XR
authors: Dai
authors: Ling
authors: L
authors: He
authors: Zhi-yu
authors: ZY
authors: Li
authors: Cong
authors: C
authors: Cao
authors: Yong
authors: Y
authors: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019556:COS Cells; D002176:Candida albicans / Q000187:drug effects*; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D053486:Melanocortins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044102:Receptor, Melanocortin, Type 1 / Q000276:immunology; D014621:Vagina / Q000187:drug effects / Q000276:immunology / Q000382:microbiology
chemical_list: D000893:Anti-Inflammatory Agents; D000935:Antifungal Agents; D016207:Cytokines; D053486:Melanocortins; D044102:Receptor, Melanocortin, Type 1