title: Mycotoxin-induced depletion of intracellular glutathione and altered cytokine production in the human alveolar epithelial cell line A549.
abstract: Mould exposure has been associated with asthma and other inflammatory airway conditions. However, cellular effects of inhaled mould components are not well understood. We hypothesised that host defence mechanisms, such as production of cytokines (TGFbeta1, IL-6 and IL-8) and the intracellular antioxidant glutathione (GSH), could be adversely affected by different concentrations of mycotoxins. We studied the effects of citrinin and gliotoxin on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (A549). Cytokines in cell culture supernatants were analysed by ELISA and levels of GSH were measured by colorimetric (absorbance) determination. We found that GSH decreased in a dose- and time-dependent manner when cells were exposed to citrinin in particular. TGFbeta1 was moderately reduced at low mycotoxin concentrations but elevated at higher sub-toxic concentrations. A tendency for an inverse relationship between TGFbeta1 and GSH levels was observed. IL-6 and IL-8 were not significantly reduced at non-toxic mycotoxin concentrations. Thus, reduced epithelial GSH and TGFbeta1 levels combined with elevated IL-6 and IL-8 levels may result in increased pro-inflammatory activity during mycotoxin exposure. We suggest that this mechanism can contribute to inflammation in mould exposure.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway. Lene.Johannessen@ntnu.no
authors.forename: L N
authors.initials: LN
authors.lastname: Johannessen
authors.forename: A M
authors.initials: AM
authors.lastname: Nilsen
authors.forename: M
authors.initials: M
authors.lastname: Løvik
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D009183:Mycotoxins / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009183:Mycotoxins; D053773:Transforming Growth Factor beta1; D005978:Glutathione