title: Endocrine disruptors found in food contaminants enhance allergic sensitization through an oxidative stress that promotes the development of allergic airway inflammation.
abstract: In the past few decades, there has been a significant increase in incidence of allergic diseases. The hygiene hypothesis may provide some clues to explain this rising trend, but it may also be attributable to other environmental factors that exert a proallergic adjuvant effects. However, there is limited information on the risks of developing allergic asthma and related diseases through the ingestion of environmental chemicals found in food contaminants. In the present study, we have shown that oral administration of tributyltin, used as a model environmental chemical, induced oxidative-stress status in the bronchial lymph node, mesenteric lymph node and spleen, but not in the lung, where the initial step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin exhibited heightened Th2 immunity to the allergen with more severe airway inflammation. Tributyltin also induced Treg cells apoptosis preferentially over non-Treg cells. All these effects of tributyltin exposure were canceled by the administration of glutathione monoethyl ester. Meanwhile, tributyltin did not affect airway inflammation of mice transferred with allergen-specific Th2 cells. Collectively, these results suggest that tributyltin exerts its pathological effect during the sensitization phase through oxidative stress that enhances the development of allergic diseases. The current study dissects the pathogenic role of oxidative stress induced by oral exposure to an environmental chemical during the sensitization phase of allergic airway inflammation and would be important for developing therapeutics for prevention of allergic diseases.
authors.affiliation: Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine, Japan. Electronic address: katotaku@doc.medic.mie-u.ac.jp.
authors.forename: Takuma
authors.initials: T
authors.lastname: Kato
authors.forename: Saeko
authors.initials: S
authors.lastname: Tada-Oikawa
authors.forename: Linan
authors.initials: L
authors.lastname: Wang
authors.forename: Mariko
authors.initials: M
authors.lastname: Murata
authors.forename: Kagemasa
authors.initials: K
authors.lastname: Kuribayashi
mesh_terms: D000485:Allergens / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000139:chemically induced / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000473:pathology*; D002454:Cell Differentiation; D052244:Endocrine Disruptors / Q000633:toxicity*; D005506:Food Contamination / Q000032:analysis*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000473:pathology; D014220:Trialkyltin Compounds / Q000009:adverse effects / Q000097:blood
chemical_list: D000485:Allergens; D052244:Endocrine Disruptors; D014220:Trialkyltin Compounds; C011559:tributyltin; C042431:S-ethyl glutathione; D005978:Glutathione
keywords: Allergic asthma; BLN; Bronchial lymph node; Endocrine disruptor; Environmental chemical; GSH; GSH-MEE; Glutathione; Glutathione monoethyl ester; Oxidative stress; TBT; Th2; Tributyltin