title: Diesel exhaust particles exacerbate allergic rhinitis in mice by disrupting the nasal epithelial barrier.
abstract: BACKGROUND
  Diesel exhaust particles (DEP), traffic-related air pollutants, are considered environmental factors that affect allergic diseases adversely. However, the exact effect of DEP on allergic rhinitis (AR) is unclear.
  
  
  OBJECTIVE
  We thought to investigate the effect of DEP on seasonal AR using a mouse model.
  
  
  METHODS
  Ragweed-pollen-sensitized mice were nasally challenged with ragweed pollen in the presence or absence of DEP. The frequency of sneezing was evaluated immediately after each nasal challenge. The expression of a tight junction (TJ) protein, zonula occludens-1 (ZO-1), was examined by immunohistochemistry in AR mice. RPMI 2650 cells were used for in vitro examination of paracellular permeability.
  
  
  RESULTS
  Mice challenged with ragweed pollen plus DEP showed increased frequency of sneezing compared with mice challenged with pollen alone. Interestingly, intranasal DEP pretreatment before ragweed pollen challenge increased ragweed-pollen-induced sneezing to levels comparable with the co-administration group. In vitro examination revealed that DEP reduced ZO-1 expression in RPMI 2650 cells. In addition, intranasal administration of DEP, but not ragweed pollen, disrupted nasal mucosal TJs in vivo. The effect of a single DEP treatment on ragweed-induced sneezing and ZO-1 expression persisted for at least 4 days and was inversely correlated. Finally, an antioxidant substance, N-acetyl-L-cysteine, inhibited DEP-mediated TJ disruption and exacerbation of sneezing in AR.
  
  
  CONCLUSIONS
  DEP disrupts TJs by a reactive oxygen species-mediated pathway, leading to the increased permeability of nasal epithelial cells. This may result in the promotion of allergen delivery into subepithelial tissues contributing to the exacerbation of immediate allergic responses.
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Fukuoka
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.|Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medical Science, University of Fukui, Fukui, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Environmental Health Division, Department of Environmental Engineering, Graduate School of Engineering, Kyoto University, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takano
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.|Department of Immunology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yoshimoto
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000485:Allergens / Q000276:immunology; D031164:Ambrosia / Q000009:adverse effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D007114:Immunization; D051379:Mice; D009297:Nasal Mucosa / Q000276:immunology* / Q000473:pathology*; D052638:Particulate Matter / Q000009:adverse effects*; D010539:Permeability; D011058:Pollen / Q000276:immunology; D065631:Rhinitis, Allergic / Q000175:diagnosis* / Q000209:etiology*; D019108:Tight Junctions; D001335:Vehicle Emissions / Q000633:toxicity
chemical_list: D000393:Air Pollutants; D000485:Allergens; D000975:Antioxidants; D052638:Particulate Matter; D001335:Vehicle Emissions
keywords: allergic rhinitis; antioxidant; diesel exhaust particles; nasal epithelial cells; reactive oxygen species; tight junctions