Epidemiological studies have shown that exposure to ambient fine
particulate matter (PM2.5 ) is associated with
respiratory diseases.
Lung inflammation is a central feature of many
pulmonary diseases, which can be induced by PM2.5 exposure. However, the mechanisms underlying PM2.5 -induced
lung inflammation remain unclear. To characterize the role of
epidermal growth factor receptor (EGFR) and
inflammasome in PM2.5 -induced
lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM2.5
suspension (4.0 mg/kg b.w.) for 5 consecutive days, respectively. Bronchoalveolar lavage (BAL) was conducted and BAL fluid (BALF) was collected. The levels of
reactive oxygen species (ROS),
inducible nitric oxide synthase (iNOS),
epidermal growth factor (
EGF), CXCL1,
interleukin (IL)-1β, and
IL-18 in BALF were determined using ELISA.
mRNA levels of
IL-6, IL-1β,
IL-18, CXCL1,
IL-10, NLRP3, Caspase-1, and NLRP12 in lung tissues were determined by RT-PCR. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) in lung tissues were examined using immunohistochemical staining and Western blotting, respectively.
Protein levels of Caspase-1, NLRP3, NF-κB-p52/p100, and NF-κB-p65 in bronchial epithelium were examined using immunohistochemical staining. It was shown that PM2.5 exposure induced
lung inflammation. Levels of total
protein, ROS, iNOS,
EGF, and CXCL1 and cell number in the BALF of mice exposed to PM2.5 were markedly elevated relative to the control.
mRNA levels of CXCL1, IL-1β, and
IL-18 in lung tissues of PM2.5 -exposed mice were increased in comparison with the control. However, level of NLRP12
mRNA in lung tissues of PM2.5 -exposed mice was reduced. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) levels in the lungs of PM2.5 -instilled mice were higher than those in the lungs of the control. The
protein levels of NF-κB-p52/p100 and NF-κB-p65 in bronchial epithelium of PM2.5 -exposed mice were also increased compared with the control. This study suggests that
EGF-EGFR-Akt-NF-κB signaling and NLRP12
inflammasome may be associated with PM2.5 -induced
lung inflammation in mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1121-1134, 2017.