title: Synergistic proinflammatory interactions of microbial toxins and structural components characteristic to moisture-damaged buildings.
abstract: Indoor exposure to microbes and their structural and metabolic compounds is notoriously complex. To study proinflammatory interactions between the multiple microbial agents, macrophages derived from human THP-1 monocytic cells were exposed to several concentrations of microbial toxins alone (emodin, enniatin B, physcion, sterigmatocystin, valinomycin) and in combination with microbial structural components (bacterial lipopolysaccharide [LPS] or fungal β-glucan). While the expression of proinflammatory cytokines TNFα and IL-1β to single toxins alone was modest, low-dose co-exposure with structural components increased the responses of emodin, enniatin B, and valinomycin synergistically, both at the mRNA and protein level, as measured by RT-qPCR and ELISA, respectively. Co-exposure of toxins and β-glucan resulted in consistent synergistically increased expression of several inflammation-related genes, while some of the responses with LPS were also inhibitory. Co-exposure of toxins with either β-glucan or LPS induced also mitochondrial damage and autophagocytosis. The results demonstrate that microbial toxins together with bacterial and fungal structural components characteristic to moisture-damaged buildings can have drastic synergistic proinflammatory interactions at low exposure levels.
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Korkalainen
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Täubel
authors.affiliation: Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Naarala
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Kirjavainen
authors.affiliation: SIB Labs, University of Eastern Finland, Kuopio, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Koistinen
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Hyvärinen
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Komulainen
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.|Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Viluksela
mesh_terms: D016902:Air Pollution, Indoor / Q000032:analysis*; D001419:Bacteria / Q000378:metabolism*; D047630:Depsipeptides / Q000378:metabolism; D004642:Emodin / Q000031:analogs & derivatives / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005658:Fungi / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D060888:Real-Time Polymerase Chain Reaction; D013241:Sterigmatocystin / Q000378:metabolism; D000074084:THP-1 Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014634:Valinomycin / Q000378:metabolism; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D047630:Depsipeptides; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; C100264:enniatins; D013241:Sterigmatocystin; D014634:Valinomycin; C008905:physcione; D004642:Emodin
keywords: Co-exposure; lipopolysaccharide; microbial toxins; proinflammatory cytokines; synergistic interaction; β-glucan