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茎菠萝蛋白酶诱导巨噬细胞凋亡和激活可减少结核分枝杆菌的持续存在。

Stem bromelain-induced macrophage apoptosis and activation curtail Mycobacterium tuberculosis persistence.

机构信息

Institute of Microbial Technology, Chandigarh, India.

出版信息

J Infect Dis. 2012 Aug 1;206(3):366-76. doi: 10.1093/infdis/jis354. Epub 2012 May 21.

DOI:10.1093/infdis/jis354
PMID:22615313
Abstract

BACKGROUND

Mycobacterium tuberculosis, the causative agent of tuberculosis, has a remarkable ability to usurp its host's innate immune response, killing millions of infected people annually. One approach to manage infection is prevention through the use of natural agents. In this regard, stem bromelain (SBM), a pharmacologically active member of the sulfhydryl proteolytic enzyme family, obtained from Ananas comosus and possessing a remarkable ability to induce the innate and acquired immune systems, is important.

METHODS

We evaluated SBM's ability to induce apoptosis and free-radical generation in macrophages. We also studied antimycobacterial properties of SBM and its effect on foamy macrophages.

RESULTS

SBM treatment of peritoneal macrophages resulted in the upregulation of proapoptotic proteins and downregulation of antiapoptotic proteins. Additionally, SBM treatment activated macrophages, curtailed the levels of free glutathione, and augmented the production of hydrogen peroxide, superoxide anion, peroxynitrite, and nitric oxide. SBM cleaves CD36 and reduced the formation of foam cells, the hallmark of M. tuberculosis infection. These conditions created an environment for the increased clearance of M. tuberculosis.

CONCLUSIONS

Together these data provide a mechanism for antimycobacterial activity of SBM and provide important insights for the use of cysteine proteases as immunomodulatory agents.

摘要

背景

结核分枝杆菌是结核病的病原体,它具有一种非凡的能力,可以篡夺宿主的先天免疫反应,每年导致数百万人感染。管理感染的一种方法是通过使用天然物质进行预防。在这方面,来自菠萝的茎菠萝蛋白酶(SBM)是一种具有巯基蛋白水解酶家族的药理活性成员,它具有显著诱导先天和获得性免疫系统的能力,非常重要。

方法

我们评估了 SBM 诱导巨噬细胞凋亡和自由基生成的能力。我们还研究了 SBM 的抗分枝杆菌特性及其对泡沫巨噬细胞的影响。

结果

SBM 处理腹腔巨噬细胞导致促凋亡蛋白上调和抗凋亡蛋白下调。此外,SBM 处理激活了巨噬细胞,降低了游离谷胱甘肽的水平,并增加了过氧化氢、超氧阴离子、过氧亚硝酸盐和一氧化氮的产生。SBM 切割 CD36 并减少泡沫细胞的形成,这是结核分枝杆菌感染的标志。这些条件为结核分枝杆菌的清除创造了有利的环境。

结论

这些数据共同为 SBM 的抗分枝杆菌活性提供了一种机制,并为使用半胱氨酸蛋白酶作为免疫调节剂提供了重要的见解。

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