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Published on: July 12, 2024
Epidermal growth factor receptor (EGFR)-MAPK-nuclear factor(NF)-κB-IL8: A possible mechanism of particulate
Seung-Chan Jeong1,2, Yoon Cho1, Mi-Kyung Song3
1Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology, P.O. Box 131, Cheongryang, Seoul, 130-650, Korea.
Abstract:
Airway inflammation plays a central role in the pathophysiology of diverse pulmonary diseases. In this study, we investigated whether exposure to particulate matter (PM) 2.5, a PM with an aerodynamic diameter of less than 2.5 µm, enhances inflammation-related toxicity in the human respiratory system through activation of the epidermal growth factor receptor (EGFR) signaling pathway. Through cytokine antibody array analysis of two extracts of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] exposed to A549 (human alveolar epithelial cell), we identified eight cytokines changed their expression with W-PM2.5 and three cytokines with O-PM2.5 . Among them, epidermal growth factor (EGF) was commonly up-regulated by W-PM2.5 and O-PM2.5 . Then, in both groups, we can identify the increase in EGF receptor protein levels. Likewise, increases in the phosphorylation of ERK1/2 MAP kinase and acetylation of nuclear factor(NF)-κB were detected. We also detected an increase in IL-8 that was related to inflammatory response. And using the erlotinib as an inhibitor of EGFR, we identified the erlotinib impaired the phosphorylation of EGFR, ERK1/2, acetylation of NF-κB proteins and decreased IL-8. Furthermore, at in vivo model, we were able to identify similar patterns. These results suggest that PM2.5 may contribute to an abnormality in the human respiratory system through EGFR, MAP kinase, NF-κB, and IL-8 induced toxicity signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1628-1636, 2017.
Insights
Particulate matter (PM) 2.5 exposure activates the epidermal growth factor receptor (EGFR) pathway, increasing inflammation and toxicity in the respiratory system. This EGFR activation leads to downstream signaling, exacerbating lung conditions.
Area of Science:
- Environmental toxicology
- Pulmonary medicine
- Cellular signaling
Background:
- Airway inflammation is critical in lung disease pathogenesis.
- Particulate matter (PM) 2.5 is a significant environmental pollutant.
- The role of PM2.5 in respiratory toxicity via specific signaling pathways requires elucidation.
Purpose of the Study:
- To investigate if PM2.5 exposure enhances respiratory inflammation and toxicity.
- To determine the involvement of the epidermal growth factor receptor (EGFR) signaling pathway in PM2.5-induced effects.
- To explore the downstream signaling molecules affected by PM2.5.
Main Methods:
- Exposure of human alveolar epithelial cells (A549) to water-soluble (W-PM2.5) and organic-soluble (O-PM2.5) PM2.5 extracts.
- Cytokine antibody array analysis to identify changes in cytokine expression.
- Western blotting to assess protein levels and phosphorylation (EGFR, ERK1/2, NF-κB).
- In vivo studies to validate findings.
Main Results:
- PM2.5 extracts upregulated epidermal growth factor (EGF) and EGFR protein levels.
- Increased phosphorylation of ERK1/2 MAP kinase and acetylation of NF-κB were observed.
- Interleukin-8 (IL-8) levels increased, indicating an inflammatory response.
- Erlotinib (EGFR inhibitor) blocked PM2.5-induced signaling and IL-8 production.
- Similar patterns were confirmed in an in vivo model.
Conclusions:
- PM2.5 exposure activates the EGFR signaling pathway in the respiratory system.
- This activation contributes to inflammation and toxicity through MAP kinase, NF-κB, and IL-8.
- Findings suggest PM2.5 exacerbates pulmonary diseases via this signaling cascade.
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