The Severity of Lung Injury and Metabolic Disorders Induced by Ambient PM 2.5 Exposure Is Associated With Cumulative Dose

Inhal Toxicol. 2018 May;30(6):239-246. doi: 10.1080/08958378.2018.1508258. Epub 2018 Sep 24.

Abstract

Lots of epidemiological and experimental studies have found that ambient fine particulate matter (PM2.5) exposure is associated with the development of cardiopulmonary diseases, obesity and diabetes. This study focused on the effects of cumulative PM2.5 exposure on pulmonary and systemic inflammation and insulin resistance. Thirty-two 6-week-old male Balb/c mice were randomly divided into four groups (FA, PM, WEEK and DAY groups) and were continuously or intermittently exposed to concentrated PM2.5 or filtered air (FA) for four weeks using Shanghai Meteorological and Environmental Animal Exposure System ("Shanghai-METAS"). The levels of IL-6 and TNF-α in serum, bronchoalveolar lavage fluid (BALF), lung tissues and white adipose tissue (WAT) were measured. Meanwhile, the expression of NF-κB and phosphor-NF-κB in lung tissue was detected by Western blot. Glucose tolerance and insulin resistance were also determined at the end of exposure. The results found that the mice in PM group displayed moderate inflammatory cell infiltration in lung, whereas the mice in WEEK and DAY groups displayed slight inflammatory cell infiltration in lung. Compared with the mice in FA group, the mRNA expressions of IL-6 and TNF-α in lung tissue and WAT significantly increased in the mice of PM group. Importantly, IL-6 and TNF-α mRNA expressions in PM group were higher than those in WEEK and DAY groups. The protein expression of phospho-NF-κB in lung tissue showed that PM group showed the activation of NF-κB, which was higher than that in the WEEK and DAY groups. Meanwhile, the mice in PM group showed more severe glucose tolerance and insulin resistance than that in the WEEK and DAY groups. The results suggested that the reduction of PM2.5 cumulative exposure may alleviate pulmonary and adipose inflammation, insulin resistance and glucose tolerance impairment. The results provided a clue that the interruption of ambient PM2.5 exposures by systems such as indoor air purification could be of benefit to people's health.

Keywords: Fine particulate matter; NF-κB; cumulative dose; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Air Pollutants / toxicity*
  • Animals
  • Blood Glucose / drug effects
  • Bronchoalveolar Lavage Fluid / chemistry
  • Dose-Response Relationship, Drug
  • Insulin Resistance*
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury / chemically induced*
  • Lung Injury / metabolism
  • Lung Injury / pathology
  • Male
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Particulate Matter / administration & dosage
  • Particulate Matter / toxicity*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Air Pollutants
  • Blood Glucose
  • Interleukin-6
  • NF-kappa B
  • Particulate Matter
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse