Background

Ozone is one of the air-pollutant, and induces airway hyper responsiveness (AHR) and neutrophilic airway inflammation, which are a part of pathophysiology of severe asthma. Thymic stromal lymphopoietin (TSLP), an epithelial derived cytokine, is important molecule in severe asthma.

Objective

To examine whether TSLP contributes to ozone-induced pulmonary responses especially focusing on type 2-low airway inflammation.

Methods

Male wild type (WT) and TSLP receptor knockout (TSLPR-KO) mice were exposed ozone at 2 ppm for 3 hours or air. At 24 hours after ozone exposure, AHR to methacholine was measured and airway inflammation was also assessed by inflammatory cell counts, cytokine and chemokine concentrations in bronchoalveolar lavage (BAL). Total protein in BAL was evaluated for examination of airway epithelial injury.

Results

WT mice showed significantly increasing of AHR by ozone and neutrophils in BAL compared to air exposed mice (p < 0.01 respectively). In ozone exposed mice, AHR was significantly attenuated in TSLPR KO mice compared to WT mice (Figure) and neutrophils in BAL was also decreased (17.0 ± 7.3 vs 5.4 ± 1.6×10⁴/ml). CCL11, IL-5, IL-13 CCL2, G-CSF, IL-6, LIF, CXCL9 and total protein in BAL were significantly increased by ozone in WT mice and those were attenuated in TSLPR-KO mice in condition of ozone exposure (p < 0.01, all).

Conclusions

These data suggested that ozone augments AHR and neutrophilic airway inflammation with increasing of type 2 and non-type 2 cytokines and airway epithelial injury.Those phenomena were regulated by TSLP which indicated that blocking of TSLP signaling might attenuate AHR and neutrophilic airway inflammation with protection of airway injury.