Association of EGF Receptor and NLRs signaling with Cardiac Inflammation and Fibrosis in Mice Exposed to Fine Particulate Matter

Abstract

ЄAmbient fine particulate matter (PM2.5 ) could induce cardiovascular diseases (CVD), but the mechanism remains unknown. To investigate the roles of epidermal growth factor receptor (EGFR) and NOD-like receptors (NLRs) in PM2.5 -induced cardiac injury, we set up a BALB/c mice model of PM2.5 -induced cardiac inflammation and fibrosis with intratracheal instillation of PM2.5 suspension (4.0 mg/kg b.w.) for 5 consecutive days (once per day). After exposure, we found that mRNA levels of CXCL1, interleukin (IL)-6, and IL-18 were elevated, but interestingly, mRNA level of NLRP12 was significant decreased in heart tissue from PM2.5 -induced mice compared with those of saline-treated mice using real-time PCR. Protein levels of phospho-EGFR (Tyr1068), phospho-Akt (Thr308), NLRP3, NF-κB-p52/p100, and NF-κB-p65 in heart tissue of PM2.5 -exposed mice were all significantly increased using immunohistochemistry or Western blotting. Therefore, PM2.5 exposure could induce cardiac inflammatory injury in mice, which may be involved with EGFR/Akt signaling, NLRP3, and NLRP12.

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

“…On one hand, a large number of inflammatory cells were discovered in PM 2.5 ‐exposed cardiac tissues, and similar pathological changes in cardiac tissues induced by PM 2.5 were also reported by a latest study . On the other hand, we found the upregulation of fibrosis area and the expression of fibrotic marker α‐SMA in the cardiac tissues of PM 2.5 ‐exposed mice compared with saline‐exposed mice, which were also confirmed by other reports …”

“…Some studies showed that mice stimulated by PM 2.5 could induce inflammation in cardiac tissues by the upregulation of IL‐1β protein and the level of IL‐1β protein in the heart failure (HF) patients was significantly higher than non‐HF patients, these reports along with our current results revealed that increased IL‐1β played a crucial role in PM 2.5 ‐induced cardiac injury. However, our previous study showed that there was no significant difference in the level of IL‐1β mRNA between PM 2.5 ‐ and saline‐induced mice . This may be related to the complex regulation mechanism from gene to protein, such as noncoding RNAs, or the peak levels of gene transcription and protein translation may be not at the same time point, which we will explore further.…”

“…To date, it has been demonstrated that active NLRP3 inflammasome is involved in the inflammatory response of respiratory system induced by particulate matter . 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 .…”

“…21,22 As to cardiovascular system, NLRP3 inflammasome has been given its possible involvement in PM 2.5 -induced heart injury in our previous research. 23 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. 24 And, the expression of NLRP3 protein may be prepared for inflammasome activation, but it is not the marker of NLRP3 inflammasome activation.…”

“…Twenty mice ( n = 10/group) were first put under light anesthesia with isoflurane and then were administered with intratracheal instillation. The dose of PM 2.5 (4.0 mg/kg BW) used in this study was determined by our previously published studies . Each mouse was treated with PM 2.5 (4.0 mg/kg BW) or saline once a day for five consecutive days.…”