Allergy Asthma Immunol Res.  2016 May;8(3):246-256. 10.4168/aair.2016.8.3.246.

Long-Term Effects of Diesel Exhaust Particles on Airway Inflammation and Remodeling in a Mouse Model

• Kim BG
• Lee PH
• Lee SH
• Kim YE
• Shin MY
• Kang Y
• Bae SH
• Kim MJ
• Rhim T
• Park CS
• Jang AS

• KMID: 2391045
• DOI: http://doi.org/10.4168/aair.2016.8.3.246

Abstract

PURPOSE
Diesel exhaust particles (DEPs) can induce and trigger airway hyperresponsiveness (AHR) and inflammation. The aim of this study was to investigate the effect of long-term DEP exposure on AHR, inflammation, lung fibrosis, and goblet cell hyperplasia in a mouse model.
METHODS
BALB/c mice were exposed to DEPs 1 hour a day for 5 days a week for 3 months in a closed-system chamber attached to a ultrasonic nebulizer (low dose: 100 microg/m3 DEPs, high dose: 3 mg/m3 DEPs). The control group was exposed to saline. Enhanced pause was measured as an indicator of AHR. Animals were subjected to whole-body plethysmography and then sacrificed to determine the performance of bronchoalveolar lavage and histology.
RESULTS
AHR was higher in the DEP group than in the control group, and higher in the high-dose DEP than in the low-dose DEP groups at 4, 8, and 12 weeks. The numbers of neutrophils and lymphocytes were higher in the high-dose DEP group than in the low-dose DEP group and control group at 4, 8, and 12 weeks. The levels of interleukin (IL)-5, IL-13, and interferon-gamma were higher in the low-dose DEP group than in the control group at 12 weeks. The level of IL-10 was higher in the high-dose DEP group than in the control group at 12 weeks. The level of vascular endothelial growth factor was higher in the low-dose and high-dose DEP groups than in the control group at 12 weeks. The level of IL-6 was higher in the low-dose DEP group than in the control group at 12 weeks. The level of transforming growth factor-beta was higher in the high-dose DEP group than in the control group at 4, 8, and 12 weeks. The collagen content and lung fibrosis in lung tissue was higher in the high-dose DEP group at 8 and 12 weeks.
CONCLUSIONS
These results suggest that long-term DEP exposure may increase AHR, inflammation, lung fibrosis, and goblet cell hyperplasia in a mouse model.

Keyword

Chronic; diesel exhaust particles; airway remodeling

MeSH Terms

Airway Remodeling
Animals
Bronchoalveolar Lavage
Collagen
Fibrosis
Goblet Cells
Hyperplasia
Inflammation*
Interferon-gamma
Interleukin-10
Interleukin-13
Interleukin-6
Interleukins
Lung
Lymphocytes
Mice*
Nebulizers and Vaporizers
Neutrophils
Plethysmography
Pneumonia
Ultrasonics
Vascular Endothelial Growth Factor A
Vehicle Emissions*
Collagen
Interferon-gamma
Interleukin-10
Interleukin-13
Interleukin-6
Interleukins
Vascular Endothelial Growth Factor A
Vehicle Emissions

Figure

• 

  Fig. 1 Schematic diagram of the experimental protocol. Mice were exposed to DEPs 5 days a week for 3 months and either 100 µg/m3 or 3 mg/m3 DEPs (or saline as a control) using an ultrasonic nebulizer.

• 

  Fig. 2 Effect of DEP exposure on airway responsiveness in mice. **P<0.01 vs the sham group; †P<0.01 vs the sham group; ‡P<0.01 vs the low-dose DEP group.

• 

  Fig. 3 Changes in cell profiles in bronchioalveolar lavage fluid. *P<0.05 vs the control group; **P<0.01 vs the control group.

• 

  Fig. 4 Effect of DEPs on IL-5 and IL-13 levels in BAL fluid. Bars represent mean±SEM from the 6 independent experiments. *P<0.05 vs the sham group.

• 

  Fig. 5 Effect of DEP on IFN-γ level in BAL fluid. Bars represent mean±SEM from the 6 independent experiments. *P<0.05 vs the sham group.

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  Fig. 6 Effect of DEP on IL-10 level in BAL fluid. Bars represent mean±SEM from the 6 independent experiments. *P<0.05 vs the sham group.

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  Fig. 7 Effect of DEP on VEGF level in BAL fluid. Bars represent mean±SEM from the 6 independent experiments. *P<0.05 vs the sham group.

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  Fig. 8 Effect of DEP on IL-6 (A) and TGF-β (B) levels in BAL fluid. Bars represent mean±SEM from the 6 independent experiments. *P<0.05 vs the sham group.

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  Fig. 9 Lung fibrosis as shown by (A) Masson trichrome staining, (B) % area, and (C) collagen content. *P<0.05 vs the control group.

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  Fig. 10 Goblet cell hyperplasia in the lung based on periodic acid-Schiff staining.

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