Epidermal growth factor receptor (EGFR)MAPKnuclear factor(NF)-BIL8: A possible mechanism of particulate matter(PM) 2.5-induced lung toxicity

Authors
Jeong, Seung-ChanCho, YoonSong, Mi-KyungLee, EunilRyu, Jae-Chun
Issue Date
2017-05
Publisher
WILEY
Citation
ENVIRONMENTAL TOXICOLOGY, v.32, no.5, pp.1628 - 1636
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 mu m, 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)-B 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-B 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-B, and IL-8 induced toxicity signaling. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1628-1636, 2017.
Keywords
NF-KAPPA-B; OVERCOMING ERLOTINIB RESISTANCE; KINASE SIGNALING PATHWAYS; EGFR MUTATION; EXPRESSION; CANCER; CELLS; PHOSPHORYLATION; ACTIVATION; PM2.5; NF-KAPPA-B; OVERCOMING ERLOTINIB RESISTANCE; KINASE SIGNALING PATHWAYS; EGFR MUTATION; EXPRESSION; CANCER; CELLS; PHOSPHORYLATION; ACTIVATION; PM2.5; Cytokine; epidermal growth factor receptor (EGFR); erlotinib; mitogen-activated protein kinase (MAPK); particulate matter2; 5(PM2; 5)
ISSN
1520-4081
URI
https://pubs.kist.re.kr/handle/201004/122795
DOI
10.1002/tox.22390
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KIST Article > 2017
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