NO2 inhalation enhances asthma susceptibility in a rat model

Abstract

Nitrogen dioxide (NO) is a major air pollutant. Epidemiologic studies have found that NO exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m NO (28 days, 5 h/day). The results showed that NO exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like features. Secondly, male Wistar rats were exposed to 5 mg/m NO (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO exposure aggravated lung inflammation in the OVA-sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO exposure promoted the increase in the expression of mucin gene (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1β, intercellular adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific immunoglobulin E (IgE) production. Taken together, we established that NO exposure promotes allergic airway inflammation and increases the asthma susceptibility. The underlying mechanisms involve the promotion of activation of interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) α, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-regulated kinase (ERK)1/2, and nuclear factor-κB (NF-κB)]. In particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon (IFN)-γ, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] plays a pivotal role in NO-induced inflammatory responses. These findings may provide a better understanding of mechanism of NO-associated respiratory diseases.

Air Pollution and Asthma

“…31 There is also mechanistic evidence showing the capacity of gaseous pollutants to enhance pro-allergenic immune pathways. 32 Epidemiologic studies support this mechanistic research. For example, Patel et al 33 found that proximity to major roads was associated with increased serum total IgE in young children in New York City, whereas Rage et al 34 found an association between ozone concentrations at residential addresses and total IgE in adults with asthma in France.…”

“…54 Allergic sensitization and Th2-biasing of immune responses itself increase susceptibility to viral respiratory infections. 3,4 However, air pollution also has multiple actions to increase susceptibility to and harm from respiratory tract infections (Table 1 26,32,[55][56][57][58] ).…”

The short-term effects of air pollution on respiratory diseases and lung cancer mortality in Hefei: A time-series analysis

“…Previous study showed that particulate matter exposure induced inflammatory cell infiltration and hyperemia in the lung tissues, increased the inflammatory cell numbers and promoted the expression of pro-inflammatory mediators (TNF-α, IL-1β, IL-6) [39]. Some studies have shown that gaseous pollutants (SO 2, NO 2 ) exposure could induce pulmonary inflammatory response and pulmonary pathological changes [46,47].…”

Risk of temperature, humidity and concentrations of air pollutants on the hospitalization of AECOPD

“…A study showed that when Sprague-Dawley rats exposed to SO 2 acutely, acute inflammation with neutrophil and macrophage airway infiltration was presented and inflammatory infiltrates remained in lung tissue for at least 14 days[6]. Previous research has established that NO2 exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in control group[7]. It was reported that sex differences in acute O3-induced airway physiology responses and airspace influx without significant difference in other injury and inflammation measures[8].…”