Zerin Tamanna, Lee Minjung, Jang Woong Sik, Nam Kung-Woo, Song Ho-Yeon
Department of Microbiology, School of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
Regional Innovation Center, Soonchunhyang University, Asan 336-745, Korea.
Mol Cells. 2015 Jul;38(7):610-5. doi: 10.14348/molcells.2015.2328. Epub 2015 Jun 18.
Alveolar epithelial cells have been functionally implicated in Mycobacterium tuberculosis infection. This study investigated the role of ursolic acid (UA)-a triterpenoid carboxylic acid with potent antioxidant, anti-tumor, anti-inflammatory, and anti-tuberculosis properties in mycobacterial infection of alveolar epithelial A549 cells. We observed that M. tuberculosis successfully entered A549 cells. Cytotoxi-city was mediated by nitric oxide (NO). A549 toxicity peaked along with NO generation 72 h after infection. The NO generated by mycobacterial infection in A549 cells was insufficient to kill mycobacteria, as made evident by the mycobacteria growth indicator tube time to detect (MGIT TTD) and viable cell count assays. Treatment of mycobacteria-infected cells with UA reduced the expression of inducible nitric oxide synthase, NO generation, and eventually improved cell viability. Moreover, UA was found to quench the translocation of the transcription factor, nuclear factor kappa B (NF-κB), from the cytosol to the nucleus in mycobacteria-infected cells. This study is the first to demonstrate the cytotoxic role of NO in the eradication of mycobacteria and the role of UA in reducing this cytotoxicity in A549 cells.
肺泡上皮细胞在结核分枝杆菌感染中具有功能相关性。本研究调查了熊果酸（UA）——一种具有强大抗氧化、抗肿瘤、抗炎和抗结核特性的三萜类羧酸——在肺泡上皮A549细胞的分枝杆菌感染中的作用。我们观察到结核分枝杆菌成功进入A549细胞。细胞毒性由一氧化氮（NO）介导。感染后72小时，A549毒性随NO生成达到峰值。如分枝杆菌生长指示管检测时间（MGIT TTD）和活细胞计数分析所示，A549细胞中分枝杆菌感染产生的NO不足以杀死分枝杆菌。用UA处理分枝杆菌感染的细胞可降低诱导型一氧化氮合酶的表达、NO生成，并最终提高细胞活力。此外，发现UA可抑制分枝杆菌感染细胞中转录因子核因子κB（NF-κB）从细胞质向细胞核的转位。本研究首次证明了NO在根除分枝杆菌中的细胞毒性作用以及UA在降低A549细胞中这种细胞毒性方面的作用。
