Involvement of EGF receptor signaling and NLRP12 inflammasome in fine particulate matter‐induced lung inflammation in mice

Abstract

Epidemiological studies have shown that exposure to ambient fine particulate matter (PM ) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM exposure. However, the mechanisms underlying PM -induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM -induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM 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 PM exposure induced lung inflammation. Levels of total protein, ROS, iNOS, EGF, and CXCL1 and cell number in the BALF of mice exposed to PM were markedly elevated relative to the control. mRNA levels of CXCL1, IL-1β, and IL-18 in lung tissues of PM -exposed mice were increased in comparison with the control. However, level of NLRP12 mRNA in lung tissues of PM -exposed mice was reduced. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) levels in the lungs of PM -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 PM -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 PM -induced lung inflammation in mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1121-1134, 2017.

Tudor‑staphylococcal nuclease regulates the expression and biological function of alkylglycerone phosphate synthase via nuclear factor‑κB and microRNA‑127 in human glioma U87MG cells

“…AGPS and Tudor-SN serve a key role in the adjustment of tumor angiogenesis, and are expressed highly in multiple tumor tissue types and are associated with the prognosis of patients (16). In the present study, it was determined that AGPS silencing or suppression inhibited the proliferation and migration of glioma U87MG cells, validating the biological function of AGPS in glioma (17).…”

NLRP3 inflammasome activation is associated with PM2.5‐induced cardiac functional and pathological injury in mice

“…The PM 2.5 suspension was stored at 4°C for use. The composition of PM 2.5 was determined using inductively coupled plasma‐mass spectrometry and gas chromatography‐mass spectrometry, which had been reported by our previous study …”

“…As to cardiovascular system, NLRP3 inflammasome has been given its possible involvement in PM 2.5 ‐induced heart injury in our previous research . In the previous study, we found the upregulation of NLRP3 protein using IHC and IL‐18 mRNA that may be regulated by NF‐KB signal pathway with RT‐PCR in PM 2.5 ‐induced cardiac tissues . And, the expression of NLRP3 protein may be prepared for inflammasome activation, but it is not the marker of NLRP3 inflammasome activation .…”

The involvement of Nox4 in fine particulate matter exposure-induced cardiac injury in mice

“…As known to all, the particles aggregate easily in sterile saline. For this reason, the PM 2.5 suspension was sonicated to make particles dispersed just before intratracheal instillation into mice (Farina et al, 2011;Jin et al, 2017). We also determined that the chemical composition of PM 2.5 samples was rich in some metals such as Zn, Al, Pb, Fe and part of PAHs.…”