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

Abstract

PurposeDiesel 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.MethodsBALB/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 µg/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.ResultsAHR 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-γ 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-β 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.ConclusionsThese results suggest that long-term DEP exposure may increase AHR, inflammation, lung fibrosis, and goblet cell hyperplasia in a mouse model.

Toluene diisocyanate exposure induces airway inflammation of bronchial epithelial cells via the activation of transient receptor potential melastatin 8

“…12 The asthmatic airway epithelium is a major source of other cytokines and chemokines, and increased susceptibility to injury and altered repair are important for both airway remodeling and the mucous metaplastic responses in patients with chronic asthma. 13, 14 …”

Comment on "Long-Term Effects of Diesel Exhaust Particles on Airway Inflammation and Remodeling in a Mouse Model" by Kim et al.

“…We recently read with interest a paper by Kim et al1 describing the inflammatory, functional, and structural effects of long-term exposure to diesel exhaust particles in BALB/c mice. Their key findings were that exposure to nebulized diesel exhaust particles (DEP) for 1 hour a day, 5 days a week for 3 months resulted in increased responsiveness to methacholine, and increased neutrophils and lymphocytes in bronchoalevolar lavage fluid, altered levels of common cytokines, and increased collagen and the lung fibrosis in lung tissue.…”

“…While Penh is an attractive option for easily and repeatedly assessing some aspects of lung function in conscious animals, it is not a measure of lung mechanics or AHR and it cannot be interpreted as such. Importantly, as mice are obligate nose breathers, in a study such as that performed by Kim et al1 where animals are subjected to an inhalational insult, Penh is further influenced by the structure of the nasal passages and/or the repeated deposition of DEP-laden saline in the nose. It is feasible that the increase in Penh measured by the authors is at least partially a result of deposition of DEP in the nose rather than in the respiratory tract.…”

“…For example, in Fig. 2 of Kim et al,1 what does a Penh measurement of ~3 for the high dose group mean in relation to a Penh measurement of ~1 for control animals? It does not mean a tripling of lung resistance, and it does not necessarily mean that any increase in lung/airway resistance is occurring.…”

“…In summary, while the work of Kim et al1 should be commended for expanding the body of knowledge on DEP health effects, limitations in the methodologies used mean that caution should be used in interpreting the results and ultimately the conclusions drawn.…”