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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Anti-Inflammatory Agents / chemistry
-
Anti-Inflammatory Agents / pharmacology*
-
Anti-Inflammatory Agents / therapeutic use
-
Antifungal Agents / chemistry
-
Antifungal Agents / pharmacology*
-
Antifungal Agents / therapeutic use
-
COS Cells
-
Candida albicans / drug effects*
-
Candidiasis, Vulvovaginal / drug therapy*
-
Candidiasis, Vulvovaginal / immunology
-
Candidiasis, Vulvovaginal / microbiology
-
Cells, Cultured
-
Chlorocebus aethiops
-
Cytokines / immunology
-
Female
-
Humans
-
Macrophages / cytology
-
Macrophages / drug effects*
-
Macrophages / immunology
-
Macrophages / microbiology
-
Melanocortins / chemistry
-
Melanocortins / pharmacology*
-
Melanocortins / therapeutic use
-
Mice
-
Phagocytosis / drug effects
-
Rats
-
Rats, Sprague-Dawley
-
Receptor, Melanocortin, Type 1 / immunology
-
Vagina / drug effects
-
Vagina / immunology
-
Vagina / microbiology
Substances
-
Anti-Inflammatory Agents
-
Antifungal Agents
-
Cytokines
-
Melanocortins
-
Receptor, Melanocortin, Type 1
Grants and funding
This work was supported by the National Natural Science Foundation of China (Nos. 91129731 and 81072661), the Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (No. JKGZ201102), the New Century Excellent Talents Program for YY supported by Ministry of Education of China (NCET-09-0771), the Natural Science Foundation of Jiangsu Province (No. BK2012025 and BK2011632), "Major Drug Discovery" science and technology major projects of China (No. 2011ZX09102-001-20). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.