title: Ursolic Acid Activates Intracellular Killing Effect of Macrophages During Mycobacterium tuberculosis Infection.
abstract: Tuberculosis is one of the most threatening infectious diseases to public health all over the world, for which Mycobacterium tuberculosis (MTB) is the etiological agent of pathogenesis. Ursolic acid (UA) has immunomodulatory function and exhibits antimycobacterial activity. However, the intracellular killing effect of UA has yet to be elucidated. The aim of this study was to evaluate the intracellular killing effect of UA during mycobacterial infection. The intracellular killing activity of UA was evaluated in the macrophage cell line THP-1 by the MGIT 960 system as well as by CFU count. The production of reactive oxygen species (ROS) and the level of nitric oxide (NO) were measured using DCF-DA and Griess reagent, respectively. Phagocytosis was observed by a fluorescence-based staining method, and the colony forming units were enumerated on 7H11 agar medium following infection. In addition, MRP8 mRNA expression was measured by qRT-PCR. UA significantly decreased the number of intracellular Mycobacterium through generation of ROS and NO. In addition, it profoundly activated the phagocytosis process of THP-1 cells during MTB-infection. Furthermore, our data demonstrated that UA activated the phagocytosis process in human monocyte cells through MRP8 induction. These data suggest that UA firmly contributes to the intracellular killing effect of macrophages during mycobacterial infection.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Podder
authors.affiliation: Regional Innovation Center, Soonchunhyang University, Asan 336-745, Republic of Korea.
authors.forename: Woong Sik
authors.initials: WS
authors.lastname: Jang
authors.affiliation: Department of Life Science and Biotechnology, Soonchunhyang University, Ansan 336-745, Republic of Korea.
authors.forename: Kung-Woo
authors.initials: KW
authors.lastname: Nam
authors.affiliation: Department of Chemistry, Soonchunhyang University, Asan 336-745, Republic of Korea.
authors.forename: Byung-Eui
authors.initials: BE
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan 330-090, Republic of Korea.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000995:Antitubercular Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000382:microbiology; D007538:Isoniazid / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D017382:Reactive Oxygen Species; D012293:Rifampin / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology*; D014376:Tuberculosis; D000097245:Ursolic Acid
chemical_list: D018528:ATP-Binding Cassette Transporters; D000995:Antitubercular Agents; D007538:Isoniazid; D017382:Reactive Oxygen Species; D012293:Rifampin; D014315:Triterpenes; D000097245:Ursolic Acid; C435500:ABCC11 protein, human