title: Lithium inhibits growth of intracellular Mycobacterium kansasii through enhancement of macrophage apoptosis.
abstract: Mycobacterium kansasii (Mk) is an emerging pathogen that causes a pulmonary disease similar to tuberculosis. Macrophage apoptosis contributes to innate host defense against mycobacterial infection. Recent studies have suggested that lithium significantly enhances the cytotoxic activity of death stimuli in many cell types. We examined the effect of lithium on the viability of host cells and intracellular Mk in infected macrophages. Lithium treatment resulted in a substantial reduction in the viability of intracellular Mk in macrophages. Macrophage cell death was significantly enhanced after adding lithium to Mk-infected cells but not after adding to uninfected macrophages. Lithium-enhanced cell death was due to an apoptotic response, as evidenced by augmented DNA fragmentation and caspase activation. Reactive oxygen species were essential for lithium-induced apoptosis. Intracellular scavenging by N-acetylcysteine abrogated the lithium-mediated decrease in intracellular Mk growth as well as apoptosis. These data suggest that lithium is associated with control of intracellular Mk growth through modulation of the apoptotic response in infected macrophages.
authors.affiliation: Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, 301-747, Republic of Korea.
authors.forename: Hosung
authors.initials: H
authors.lastname: Sohn
authors.forename: Kwangwook
authors.initials: K
authors.lastname: Kim
authors.forename: Kil-Soo
authors.initials: KS
authors.lastname: Lee
authors.forename: Han-Gyu
authors.initials: HG
authors.lastname: Choi
authors.forename: Kang-In
authors.initials: KI
authors.lastname: Lee
authors.forename: A-Rum
authors.initials: AR
authors.lastname: Shin
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Song
authors.forename: Jeong-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007155:Immunologic Factors / Q000378:metabolism*; D008094:Lithium / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000187:drug effects; D019909:Mycobacterium kansasii / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D017382:Reactive Oxygen Species; D008094:Lithium