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 and clinical relevance: 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.

Keywords: allergic rhinitis; antioxidant; diesel exhaust particles; nasal epithelial cells; reactive oxygen species; tight junctions.