The synthetic melanocortin (CKPV)2 exerts anti-fungal and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization.

The synthetic melanocortin (CKPV)2 exerts anti-fungal and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization.
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DOI:
10.1371/journal.pone.0056004
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Yang Y
Yang Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ji HX;Zou YL;Duan JJ;Jia ZR;Li XJ;Wang Z;Li L;Li YW;Liu GY;Tong MQ;Li XY;Zhang GH;Dai XR;He L;Li ZY;Cao C;Yang Y

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在这项研究中,我们检查了合成黑皮质素肽 (Ac-Cys-Lys-Pro-Val-NH2)2 或 (CKPV)2 对白色念珠菌阴道炎的抗真菌和抗炎作用。我们的体外结果表明,(CKPV)2 剂量依赖性地抑制白色念珠菌菌落形成。在大鼠白色念珠菌阴道炎模型中,(CKPV)2显着抑制阴道白色念珠菌存活和巨噬细胞上皮下粘膜浸润。对于机制研究,我们观察到(CKPV)2抑制巨噬细胞对白色念珠菌的吞噬作用。同时,(CKPV)2给药抑制巨噬细胞促炎细胞因子(TNF-α、IL-1β和IL-6)释放,同时增加精氨酸酶活性和抗炎细胞因子IL-10的产生,表明巨噬细胞M1至M2极化。在巨噬细胞中施用 (CKPV)2 也可诱导环化 AMP (cAMP) 的产生。 (CKPV)2 对巨噬细胞的上述影响几乎被黑皮质素受体 1 (MC1R) siRNA 敲低所逆转,表明该过程中需要 MC1R。总而言之,我们的结果表明,(CKPV)2 可能通过诱导巨噬细胞 M1 至 M2 极化和 MC1R 激活而对白色念珠菌阴道炎发挥抗真菌和抗炎活性。
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.
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