Abstract
One of the health hazards of PM2.5 exposure is to induce pulmonary inflammatory responses. In our previous study, we demonstrated that exposing both the immortalized and primary human bronchial epithelial cells to PM2.5 results in a significant upregulation of VEGF production, a typical signaling event to trigger chronic airway inflammation. Further investigations showed that PM2.5 exposure strongly induces ATR/CHK1/p53 cascade activation, leading to the induction of DRAM1-dependent autophagy to mediate VEGF expression by activating Src/STAT3 pathway. In the current study, we further revealed that TIGAR was another transcriptional target of p53 to trigger autophagy and VEGF upregulation in Beas-2B cells after PM2.5 exposure. Furthermore, LKB1, but not ATR and CHK1, played a critical role in mediating p53/TIGAR/autophagy/VEGF pathway activation also by linking to Src/STAT3 signaling cascade. Therefore, on combination of the previous report, we have identified both ATR/CHK1/p53/DRAM1- and LKB1/p53/TIGAR- dependent autophagy in mediating VEGF production in the bronchial epithelial cells under PM2.5 exposure. Moreover, the in vivo study further confirmed VEGF induction in the airway potentially contributed to the inflammatory responses in the pulmonary vascular endothelium of PM2.5-treated rats. Therefore, blocking VEGF expression or autophagy induction might be the valuable strategies to alleviating PM2.5-induced respiratory injuries.
Highlights
One of the health hazards of PM2.5 exposure is to induce pulmonary inflammatory responses
We demonstrated that PM2.5 exposure strongly induces VEGF expression in Beas-2B human bronchial epithelial cells, but the levels of other pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα) in the cell culture media did not show obvious differences before and after PM2.5 exposure
In the attempt to disclose the mechanism involving in VEGF induction, we observe that PM2.5 exposure induces ATR/CHK1/p53 cascade activation, leading to the induction of DRAM1-dependent autophagy to mediate VEGF transcription and secretion by activating Src/STAT3 pathway[12]
Summary
One of the health hazards of PM2.5 exposure is to induce pulmonary inflammatory responses. We demonstrated that exposing both the immortalized and primary human bronchial epithelial cells to PM2.5 results in a significant upregulation of VEGF production, a typical signaling event to trigger chronic airway inflammation. On combination of the previous report, we have identified both ATR/CHK1/p53/DRAM1- and LKB1/p53/TIGAR- dependent autophagy in mediating VEGF production in the bronchial epithelial cells under PM2.5 exposure. We demonstrate that exposing immortalized and primary human bronchial epithelial cells to PM2.5 induces p53 transactivation and autophagy, which leads to a significant upregulation of VEGF production, a typical signaling event in mediating chronic inflammation and vascular endothelial dysfunction in the lung. On combination of the previous report, we have identified both ATR/CHK1/p53/DRAM1- and LKB1/p53/TIGAR- dependent autophagy in mediating VEGF production in the bronchial epithelial cells and its contribution to the pulmonary inflammatory responses induced by PM2.5
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
