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

Chemosphere. 2015 Feb:120:722-8. doi: 10.1016/j.chemosphere.2014.10.039. Epub 2014 Nov 11.


Nitrogen dioxide (NO2) is an air pollutant associated with poor respiratory health, asthma exacerbation, and an increased likelihood of inhalational allergies. However, the underlying mechanisms are not clear. In the present study, the airway inflammatory response was first assessed in rats exposed to 5mg/m(3) NO2 for seven days. The results showed that NO2 exposure caused the pulmonary pathological alteration, and significantly stimulated MUC5AC expression. Following this, obviously up-regulated changes of pro-inflammatory cytokines (IL-1β, IL-6, and ICAM-1) were observed. Also, NO2 inhalation induced the imbalance in the ratio of Th1/Th2 differentiation (IL-4, IFN-γ, GATA-3 and T-bet) and the activation of following JAK-STAT pathway (JAK1, JAK3 and STAT6). The findings clarify an important mechanism for NO2 inhalation being injurious to the lung and augmenting the degree of allergic airway inflammation.

Keywords: Airway inflammation; JAK-STAT pathway; NO(2); Th1/Th2 differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollutants / adverse effects*
  • Analysis of Variance
  • Animals
  • Cell Differentiation / drug effects
  • Cytokines / metabolism
  • DNA Primers / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / drug effects*
  • Inflammation / chemically induced*
  • Inflammation / immunology*
  • Janus Kinase 1 / metabolism
  • Janus Kinase 3 / metabolism
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Microscopy, Electron, Transmission
  • Mucin 5AC / metabolism
  • Nitrogen Dioxide / adverse effects*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Th1-Th2 Balance / drug effects


  • Air Pollutants
  • Cytokines
  • DNA Primers
  • Jak3 protein, rat
  • Muc5ac protein, rat
  • Mucin 5AC
  • STAT6 Transcription Factor
  • Jak1 protein, rat
  • Janus Kinase 1
  • Janus Kinase 3
  • Nitrogen Dioxide