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白藜芦醇通过干扰黏附和毒素产生调节瑞替加滨毒素诱导的细胞毒性。

Resveratrol modulates RTX toxin-induced cytotoxicity through interference in adhesion and toxin production.

机构信息

Department of Oriental Medicine Materials, Dongshin University, 252 Daeho-dong, Naju, Jeonnam, 520-714, Republic of Korea.

出版信息

Eur J Pharmacol. 2010 Sep 10;642(1-3):163-8. doi: 10.1016/j.ejphar.2010.05.037. Epub 2010 Jun 9.

DOI:10.1016/j.ejphar.2010.05.037
PMID:20553907
Abstract

Host-parasite contact is a prerequisite for the acute cytotoxicity of Vibrio vulnificus, which is mediated primarily by RtxA1, a repeat in toxin (RTX) toxin. We found that resveratrol (at 10 or 30 microM), a natural polyphenol, protected HeLa cells from V. vulnificus cytotoxicity. To further characterize the underlying mechanism, the effect of resveratrol was investigated at the level of the host-microbe interactions. We studied the effects of resveratrol on adhesion, motility, cytotoxicity, and RtxA1 toxin expression of V. vulnificus. In addition, the effect of resveratrol on mouse mortality caused by V. vulnificus was investigated. Resveratrol inhibited V. vulnificus motility and the microbe adhesion to host cells, critical virulence traits for many bacteria. Resveratrol also down-regulated the expression of RtxA1 toxin at the transcriptional level and thereby protected the host cells from becoming rounded and damaged. In addition, resveratrol (20mg/kg) protected CD-1 mice from V. vulnificus infection. Taken together, these results suggest that resveratrol, a modulator of host-microbe interactions, has potential for development as a new paradigm drug to treat infectious diseases.

摘要

宿主-寄生虫接触是创伤弧菌急性细胞毒性的前提,这主要是由 RtxA1(重复毒素 RTX 毒素)介导的。我们发现白藜芦醇(10 或 30μM),一种天然多酚,可保护 HeLa 细胞免受创伤弧菌的细胞毒性。为了进一步阐明潜在的机制,我们在宿主-微生物相互作用的水平上研究了白藜芦醇的作用。我们研究了白藜芦醇对创伤弧菌黏附、运动性、细胞毒性和 RtxA1 毒素表达的影响。此外,还研究了白藜芦醇对创伤弧菌引起的小鼠死亡率的影响。白藜芦醇抑制了创伤弧菌的运动性和微生物对宿主细胞的黏附,这是许多细菌的关键毒力特征。白藜芦醇还在转录水平下调了 RtxA1 毒素的表达,从而保护宿主细胞免受变形和损伤。此外,白藜芦醇(20mg/kg)可保护 CD-1 小鼠免受创伤弧菌感染。总之,这些结果表明,白藜芦醇作为一种调节宿主-微生物相互作用的调节剂,具有开发为治疗感染性疾病的新型范式药物的潜力。

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Eur J Pharmacol. 2010 Sep 10;642(1-3):163-8. doi: 10.1016/j.ejphar.2010.05.037. Epub 2010 Jun 9.
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