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肝素与念珠菌溶血素相互作用,中和其对口腔上皮细胞的细胞毒性。

Heparin interacts with candidalysin and neutralizes its cytotoxicity to oral epithelial cells.

机构信息

Department of Biochemistry, Osaka Dental University, Hirakata, Osaka, 5731121, Japan.

Department of Biochemistry, Osaka Dental University, Hirakata, Osaka, 5731121, Japan.

出版信息

J Oral Biosci. 2023 Jun;65(2):206-210. doi: 10.1016/j.job.2023.03.002. Epub 2023 Mar 23.

Abstract

OBJECTIVES

Candidalysin is a peptide toxin produced by Candida albicans that causes damage to epithelial cells by destabilizing the plasma membrane. This study aimed to evaluate heparin's ability to neutralize candidalysin and protect epithelial cells from lysis.

METHODS

The study was conducted using a human oral epithelial cell line and synthetic candidalysin. Cell damage was assessed by measuring lactate dehydrogenase release. Enzyme-linked immunosorbent assay and immunoblotting were used to determine cytokine concentrations and assess activation of intracellular signaling molecules and transcription factors, respectively. Flow cytometry was used to measure cell-bound candidalysin.

RESULTS

Heparin diminished the cell-lytic activity of candidalysin and subsequent epithelial responses. Additionally, heparin inhibited the interaction between candidalysin and epithelial cells. Furthermore, polyacrylic acid, a synthetic polymer, mimicked the neutralizing effects of candidalysin.

CONCLUSION

Our findings suggest that negatively charged polymers could be a potential therapeutic option for preventing the damage caused by candidalysin. Further research is needed to explore the effectiveness of other anionic polymers and their potential clinical applications.

摘要

目的

念珠菌溶血素是由白念珠菌产生的一种肽毒素,通过破坏质膜导致上皮细胞损伤。本研究旨在评估肝素中和念珠菌溶血素并保护上皮细胞免受溶解的能力。

方法

该研究使用人口腔上皮细胞系和合成的念珠菌溶血素进行。通过测量乳酸脱氢酶释放来评估细胞损伤。酶联免疫吸附试验和免疫印迹分别用于测定细胞因子浓度和评估细胞内信号分子和转录因子的激活情况。流式细胞术用于测量细胞结合的念珠菌溶血素。

结果

肝素降低了念珠菌溶血素的细胞溶解活性和随后的上皮反应。此外,肝素抑制了念珠菌溶血素与上皮细胞的相互作用。此外,聚丙烯酸,一种合成聚合物,模拟了念珠菌溶血素的中和作用。

结论

我们的研究结果表明,带负电荷的聚合物可能是预防念珠菌溶血素引起的损伤的潜在治疗选择。需要进一步研究以探索其他阴离子聚合物的有效性及其潜在的临床应用。

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