title: Ursolic Acid Reduces Mycobacterium tuberculosis-Induced Nitric Oxide Release in Human Alveolar A549 cells.
abstract: 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.
authors.affiliation: Department of Microbiology, School of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
authors.forename: Tamanna
authors.initials: T
authors.lastname: Zerin
authors.affiliation: Department of Microbiology, School of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Regional Innovation Center, Soonchunhyang University, Asan 336-745, Korea.
authors.forename: Woong Sik
authors.initials: WS
authors.lastname: Jang
authors.affiliation: Department of Life Science and Biotechnology, College of Natural Science, Soonchunhyang University, Asan 336-745, Korea.
authors.forename: Kung-Woo
authors.initials: KW
authors.lastname: Nam
authors.affiliation: Department of Microbiology, School of Medicine, Soonchunhyang University, Cheonan 330-090, Korea.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D055985:Latent Tuberculosis / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology* / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Mycobacterium tuberculosis; anti-tuberculosis; inducible nitric oxide synthase (iNOS); nuclear factor kappa B (NF-κB); ursolic acid