title: Comparison of mycobacteria-induced cytotoxicity and inflammatory responses in human and mouse cell lines.
abstract: Environmental mycobacteria, which are ubiquitous in nature, are also detected in moisture-damaged buildings. Their potential role inducing the adverse health effects associated with living in moisture damaged buildings requires clarification. To establish a model for these studies, we evaluated inflammatory responsiveness in different cell lines exposed to environmental mycobacterial species. Four mycobacterial isolates belonging to Mycobacterium avium complex and Mycobacterium terrae, recovered from the indoor air sampled when a moldy building was being demolished, were studied for their cytotoxicity and ability to stimulate the production of inflammatory mediators in mouse RAW264.7 and human 28SC macrophage cell lines, and human A549 lung epithelial cell line. Lipopolysaccharide (LPS) was used as a positive control. Production of cytokines (tumor necrosis factor alpha, TNF-alpha; interleukin 6, IL-6; and interleukin beta, IL-1beta) was analyzed immunochemically, nitric oxide (NO) by the Griess method, expression of inducible NO synthase with Western blot analysis, and cytotoxicity with the MTT test. Both human and mouse cells produced NO and IL-6 after mycobacterial exposure. Mouse macrophages also showed production of TNF-alpha induced by both mycobacteria and LPS, whereas the human cell lines failed to produce TNF-alpha after mycobacterial exposure and the human epithelial cell line also failed to respond to LPS. Similarly, only mouse macrophages produced IL-1beta. Mycobacterial exposure was not cytotoxic to human cells and was only slightly cytotoxic to mouse macrophages. The results indicate that environmental mycobacterial isolates from moldy buildings are capable of activating inflammatory mechanisms in both human and murine cells. The human and mouse cell lines, however, differ significantly in the grade and type of the responses.
authors.affiliation: Division of Environmental Health, National Public Health Institute, PO Box 95, FIN-70701 Kuopio, Finland. Kati.Huttunen@ktl.fi
authors.forename: K
authors.initials: K
authors.lastname: Huttunen
authors.forename: J
authors.initials: J
authors.lastname: Jussila
authors.forename: M R
authors.initials: MR
authors.lastname: Hirvonen
authors.forename: E
authors.initials: E
authors.lastname: Iivanainen
authors.forename: M L
authors.initials: ML
authors.lastname: Katila
mesh_terms: D016902:Air Pollution, Indoor / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D004781:Environmental Exposure; D004847:Epithelial Cells / Q000276:immunology / Q000502:physiology; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000166:cytology; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D015269:Mycobacterium avium Complex; D019001:Nitric Oxide Synthase / Q000032:analysis; D009170:Nontuberculous Mycobacteria
chemical_list: D016207:Cytokines; D019001:Nitric Oxide Synthase