TY - JOUR
T1 - Epidermal growth factor receptor (EGFR)—MAPK—nuclear factor(NF)-κB—IL8
T2 - A possible mechanism of particulate matter(PM) 2.5-induced lung toxicity
AU - Jeong, Seung Chan
AU - Cho, Yoon
AU - Song, Mi Kyung
AU - Lee, Eunil
AU - Ryu, Jae Chun
N1 - Funding Information:
This study was supported by The Ecoinnovation Project (grant numbers 412-111-010), as “The Eco-Innovation Project”, and by the Korea Institute of Science and Technology (KIST) Program 2E25290 of the Republic of Korea.
Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/5
Y1 - 2017/5
N2 - 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.
AB - 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.
KW - Cytokine
KW - epidermal growth factor receptor (EGFR)
KW - erlotinib
KW - mitogen-activated protein kinase (MAPK)
KW - particulate matter2.5(PM2.5)
UR - http://www.scopus.com/inward/record.url?scp=85017569171&partnerID=8YFLogxK
U2 - 10.1002/tox.22390
DO - 10.1002/tox.22390
M3 - Article
C2 - 28101945
AN - SCOPUS:85017569171
SN - 1520-4081
VL - 32
SP - 1628
EP - 1636
JO - Environmental Toxicology
JF - Environmental Toxicology
IS - 5
ER -
