title: Exposure to mycotoxins increases the allergic immune response in a murine asthma model.
abstract: BACKGROUND
  Epidemiological studies have shown that indoor molds are associated with increased prevalence and exacerbation of respiratory symptoms and asthma. Mycotoxins, secondary metabolites of molds, may contribute to these effects.
  
  
  OBJECTIVE
  To investigate the adjuvant activity of mycotoxins on allergic airway inflammation.
  
  
  METHODS
  Balb/c mice were exposed via the airways to gliotoxin and via the intestine to patulin, sensitized with ovalbumin (OVA), and then analyzed in acute and chronic murine asthma models. In addition, the effect of mycotoxin exposure on dendritic cell (DC) function was investigated using murine bone marrow-derived DCs.
  
  
  RESULTS
  Exposure of mice to both mycotoxins enhanced dose-dependently airway hyperreactivity, eosinophilic lung inflammation, and OVA-specific IgE serum levels compared with mice that received only the antigen. These findings correlated with increased Th2 cytokine levels and decreased IFN-gamma production. Long-term mycotoxin exposure exacerbated chronic airway inflammation and airway remodeling. In vitro or in vivo mycotoxin exposure inhibited IL-12 production in maturing DCs and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. Mycotoxin exposure enhanced OVA-induced lung lipid peroxidation and moderately increased isoprostane levels in naive mice. Treatment of mycotoxin-exposed DCs with the antioxidants N-acetylcysteine or glutathione ethyl ester restored IL-12 secretion and pretreatment of exposed mice with N-acetylcysteine prevented the mycotoxin-induced increase of airway inflammation and AHR.
  
  
  CONCLUSIONS
  Our results demonstrate that gliotoxin and patulin increase the allergic immune response in mice by modulating the Th1/Th2 balance via direct effects on IL-12 secretion in DCs and by inducing oxidative stress.
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research Leipzig-Halle, Department of Environmental Immunology, Leipzig, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schütze
authors.forename: Irina
authors.initials: I
authors.lastname: Lehmann
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bönisch
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
authors.forename: Tobias
authors.initials: T
authors.lastname: Polte
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D056151:Airway Remodeling / Q000187:drug effects / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005912:Gliotoxin / Q000633:toxicity*; D005978:Glutathione / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000378:metabolism; D028421:Isoprostanes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010365:Patulin / Q000633:toxicity*; D010993:Plethysmography, Whole Body; D011042:Poisons / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014178:Translocation, Genetic / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
chemical_list: D000199:Actins; D016166:Free Radical Scavengers; D007166:Immunosuppressive Agents; D007378:Interleukins; D028421:Isoprostanes; D016328:NF-kappa B; D011042:Poisons; D018809:Proliferating Cell Nuclear Antigen; D018664:Interleukin-12; D007073:Immunoglobulin E; D005912:Gliotoxin; C042431:S-ethyl glutathione; D007371:Interferon-gamma; D010365:Patulin; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; D000111:Acetylcysteine