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抗菌十肽 KSL-W 通过调节其对 Toll 样受体、人 β-防御素和细胞因子表达的影响,减弱白念珠菌的毒力。

Antimicrobial decapeptide KSL-W attenuates Candida albicans virulence by modulating its effects on Toll-like receptor, human β-defensin, and cytokine expression by engineered human oral mucosa.

机构信息

Oral Ecology Research Group, Faculty of Dentistry, Laval University, Quebec, QC, Canada.

出版信息

Peptides. 2011 May;32(5):859-67. doi: 10.1016/j.peptides.2011.01.020. Epub 2011 Feb 2.

Abstract

We investigated the toxicity of synthetic antimicrobial decapeptide KSL-W on normal human gingival epithelial cell cultures, its effect on Candida albicans adhesion and growth, and the activation of epithelial cell innate immunity. Our results indicate that KSL-W had no toxic effect on cell adhesion or growth, suggesting its safe use with human cells. Pre-treating C. albicans with KSL-W attenuated the yeast's virulence as demonstrated by its reduced adhesion and growth on engineered human oral mucosa epithelium and the subsequent decreased expression of some innate defense molecules by targeted epithelial cells. Indeed, the expression of Toll-like receptors and human β-defensins was reduced in tissues infected with KSL-W-treated Candida. Proinflammatory cytokine secretion (IL-1β and IL-6) by the epithelial cells was also regulated by KSL-W in a manner similar to that of antifungal molecule amphotericin B. These findings therefore show that KSL-W is safe for use with human cells and is able to attenuate Candida virulence by modulating its effects on host innate immunity. This study proposes the potential application of KSL-W peptide as an alternative antifungal agent.

摘要

我们研究了合成抗菌十肽 KSL-W 对正常人类牙龈上皮细胞培养物的毒性,其对白色念珠菌黏附与生长的影响,以及上皮细胞固有免疫的激活作用。我们的结果表明,KSL-W 对细胞黏附或生长没有毒性作用,这表明它可以安全地用于人类细胞。用 KSL-W 预处理白色念珠菌可降低其毒力,这表现在酵母在工程化的人口腔黏膜上皮上的黏附和生长减少,以及随后靶向上皮细胞中某些固有防御分子的表达降低。实际上,感染了经 KSL-W 处理的白色念珠菌的组织中 Toll 样受体和人β-防御素的表达减少。上皮细胞的促炎细胞因子(IL-1β 和 IL-6)分泌也被 KSL-W 以类似于抗真菌分子两性霉素 B 的方式调节。这些发现表明,KSL-W 对人类细胞是安全的,并且能够通过调节其对宿主固有免疫的影响来减轻念珠菌的毒力。本研究提出了将 KSL-W 肽作为替代抗真菌剂的应用潜力。

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