NO2 inhalation enhances asthma susceptibility in a rat model - PubMed

Affiliations

• PMID: 28986735
• DOI: 10.1007/s11356-017-0402-7

NO₂ inhalation enhances asthma susceptibility in a rat model

Ming Han et al. Environ Sci Pollut Res Int. 2017 Dec.

Abstract

Nitrogen dioxide (NO₂) is a major air pollutant. Epidemiologic studies have found that NO₂ exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO₂ inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m³ NO₂ (28 days, 5 h/day). The results showed that NO₂ 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/m³ NO₂ (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO₂ exposure aggravated lung inflammation in the OVA-sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO₂ 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 NO₂ 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 NO₂-induced inflammatory responses. These findings may provide a better understanding of mechanism of NO₂-associated respiratory diseases.

Keywords: Airway inflammation; Allergic asthma; IL-4/STAT6 pathway; Nitrogen dioxide; Th1/Th2 differentiation.

Similar articles

• Acute nitrogen dioxide (NO2) exposure enhances airway inflammation via modulating Th1/Th2 differentiation and activating JAK-STAT pathway.

  Ji X, Han M, Yun Y, Li G, Sang N. Ji X, et al. Chemosphere. 2015 Feb;120:722-8. doi: 10.1016/j.chemosphere.2014.10.039. Epub 2014 Nov 11. Chemosphere. 2015. PMID: 25462318

• Effect of NO₂ exposure on airway inflammation and oxidative stress in asthmatic mice.

  Lu C, Wang F, Liu Q, Deng M, Yang X, Ma P. Lu C, et al. J Hazard Mater. 2023 Sep 5;457:131787. doi: 10.1016/j.jhazmat.2023.131787. Epub 2023 Jun 7. J Hazard Mater. 2023. PMID: 37295329

• Interleukin-1 receptor and caspase-1 are required for the Th17 response in nitrogen dioxide-promoted allergic airway disease.

  Martin RA, Ather JL, Lundblad LK, Suratt BT, Boyson JE, Budd RC, Alcorn JF, Flavell RA, Eisenbarth SC, Poynter ME. Martin RA, et al. Am J Respir Cell Mol Biol. 2013 May;48(5):655-64. doi: 10.1165/rcmb.2012-0423OC. Am J Respir Cell Mol Biol. 2013. PMID: 23371061 Free PMC article.

• Critical review of the human data on short-term nitrogen dioxide (NO2) exposures: evidence for NO2 no-effect levels.

  Hesterberg TW, Bunn WB, McClellan RO, Hamade AK, Long CM, Valberg PA. Hesterberg TW, et al. Crit Rev Toxicol. 2009;39(9):743-81. doi: 10.3109/10408440903294945. Crit Rev Toxicol. 2009. PMID: 19852560 Review.

• Interaction of air pollutants and pulmonary allergic responses in experimental animals.

  Gilmour MI. Gilmour MI. Toxicology. 1995 Dec 28;105(2-3):335-42. doi: 10.1016/0300-483x(95)03230-d. Toxicology. 1995. PMID: 8571370 Review.

Cited by

• Increased Weekly Mean PM_2.5, and NO₂ Are Associated With Increased Proportions of Lower Airway Granulocytes in Ontario Horses.

  Brankston G, Greer AL, Marshall Q, Lang B, Moore K, Hodgins D, Hennessey JTG, Beeler-Marfisi J. Brankston G, et al. Front Vet Sci. 2020 May 5;7:185. doi: 10.3389/fvets.2020.00185. eCollection 2020. Front Vet Sci. 2020. PMID: 32432128 Free PMC article.

• Respiratory Effects of Traffic-Related Air Pollution: A Randomized, Crossover Analysis of Lung Function, Airway Metabolome, and Biomarkers of Airway Injury.

  Zhu X, Zhang Q, Du X, Jiang Y, Niu Y, Wei Y, Zhang Y, Chillrud SN, Liang D, Li H, Chen R, Kan H, Cai J. Zhu X, et al. Environ Health Perspect. 2023 May;131(5):57002. doi: 10.1289/EHP11139. Epub 2023 May 4. Environ Health Perspect. 2023. PMID: 37141245 Free PMC article. Clinical Trial.

• Association of Daily Exposure to Air Pollutants with the Risk of Tuberculosis in Xuhui District of Shanghai, China.

  Xiong Y, Yang M, Wang Z, Jiang H, Xu N, Tong Y, Yin J, Chen Y, Jiang Q, Zhou Y. Xiong Y, et al. Int J Environ Res Public Health. 2022 May 17;19(10):6085. doi: 10.3390/ijerph19106085. Int J Environ Res Public Health. 2022. PMID: 35627622 Free PMC article.

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

  Chen C, Liu X, Wang X, Li W, Qu W, Dong L, Li X, Rui Z, Yang X. Chen C, et al. PLoS One. 2019 Nov 26;14(11):e0225307. doi: 10.1371/journal.pone.0225307. eCollection 2019. PLoS One. 2019. PMID: 31770406 Free PMC article.

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

• Full Text Sources

  • Springer

• Other Literature Sources

  • scite Smart Citations

• Medical

  • MedlinePlus Consumer Health Information
  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal