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.
Highlights
The common commensal Fungus Candida albicans cause systemic or mucocutaneous infections in abnormal immunity environments [1]
We found that (CKPV)2 played a Candidacidal role in rat Candida albicans vaginitis, and induced anti-inflammatory effects by inducing macrophages M2 polarization, activation of MC1R appeared is involved in the process
We summarized that (CKPV)2 inhibited pro-inflammatory cytokines (TNF-a, interleukin 1b (IL-1b) and IL-6) production while increasing arginase activity and the secretion of IL-10 to favor a macrophage M1 to M2 polarization
Summary
The common commensal Fungus Candida albicans cause systemic or mucocutaneous infections in abnormal immunity environments [1]. 80%–90% VVC patients are treated with imidazole drugs, which can relieve symptoms and prevent inflammations These drugs usually have side effects including itching, burning, local allergic reactions and other possible off-target toxicities. A-MSH activates MC1R and inhibits lipopolysaccharide (LPS)-induced nuclear factor kB (NF-kB). KPV could inhibit inflammation with no cAMP accumulation, suggesting that its anti-inflammatory effects may not be solely dependent on MCRs [16]. The fact that cAMP inhibitor abolished (CKPV)2’s effects on chemo-taxis and respiratory burst [20] suggests that the anti-inflammatory activity of (CKPV) may be dependent on MCRs, as similar to a-MSH. We found that (CKPV) played a Candidacidal role in rat Candida albicans vaginitis, and induced anti-inflammatory effects by inducing macrophages M2 polarization, activation of MC1R appeared is involved in the process
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