Epidermal growth factor receptor (EGFR)—MAPK—nuclear factor(NF)-κB—IL8: A possible mechanism of particulate matter(PM) 2.5-induced lung toxicity

Seung Chan Jeong, Yoon Cho, Mi Kyung Song, Eun Il Lee, Jae Chun Ryu

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1628-1636
Number of pages9
JournalEnvironmental Toxicology
Volume32
Issue number5
DOIs
Publication statusPublished - 2017 May 1

Keywords

  • Cytokine
  • epidermal growth factor receptor (EGFR)
  • erlotinib
  • mitogen-activated protein kinase (MAPK)
  • particulate matter2.5(PM2.5)

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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