Long-term exposure to PM2.5 lowers influenza virus resistance via down-regulating pulmonary macrophage Kdm6a and mediates histones modification in IL-6 and IFN-β promoter regions

Biochem Biophys Res Commun. 2017 Nov 18;493(2):1122-1128. doi: 10.1016/j.bbrc.2017.09.013. Epub 2017 Sep 5.

Abstract

Atmospheric particulates, especially PM2.5, not only damage the respiratory system, but also play important roles in pulmonary immunity. China is influenced by atmospheric diffusion conditions, industrial manufacturers, and heating and discharging. PM2.5 levels in the air rise substantially in the winter, which is also a period of flu high-incidence. Although an epidemiological link exists between PM2.5 and flu, we do not understand how long-term PM2.5 inhalation affects pulmonary immunity and the influenza virus response. Our study has prepared an in vivo PM2.5 mouse pharyngeal wall drop-in model and has found that PM2.5 exposure leads to mouse inflammatory injuries and furthers influenza A infection. Our results suggest that short-term exposure to PM2.5 significantly enhances the survival rate of influenza A-contaminated mice, while long-term PM2.5 inhalation lowers the capacity of pulmonary macrophages to secrete IL-6 and IFN-β. A disorder in the pulmonary innate defense system results in increased death rates following influenza infection. On a macromolecular level, this mechamism involves Kdm6a down-regulation after long-term exposure to PM 2.5 and a resultant increase in H3K4 and H3K9 methylation in IL-6 and IFN-β promoter regions. In summary, PM2.5 causes injuries of lung tissue cells and downregulates immune defense mechanisms in the lung.

Keywords: Histones modification; Influenza virus resistance; Kdm6a; PM2.5.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Down-Regulation
  • Histone Code
  • Histone Demethylases / genetics*
  • Histone Demethylases / immunology
  • Humans
  • Immunity, Innate
  • Influenza A virus / immunology
  • Influenza A virus / physiology*
  • Influenza, Human / etiology*
  • Influenza, Human / genetics
  • Influenza, Human / immunology
  • Influenza, Human / pathology
  • Interferon-beta / genetics*
  • Interferon-beta / immunology
  • Interleukin-6 / genetics*
  • Interleukin-6 / immunology
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lung / virology
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / pathology*
  • Macrophages, Alveolar / virology
  • Mice
  • Orthomyxoviridae Infections / etiology
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / pathology
  • Particulate Matter / adverse effects*
  • Particulate Matter / immunology
  • Promoter Regions, Genetic

Substances

  • Interleukin-6
  • Particulate Matter
  • Interferon-beta
  • Histone Demethylases
  • Utx protein, mouse