title: Epidermal growth factor receptor (EGFR)-MAPK-nuclear factor(NF)-κB-IL8: A possible mechanism of particulate matter(PM) 2.5-induced lung toxicity.
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-PM2.5and three cytokines with O-PM2.5. Among them, epidermal growth factor (EGF) was commonly up-regulated by W-PM2.5and 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 PM2.5may 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.
authors.affiliation: Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology, P.O. Box 131, Cheongryang, Seoul, 130-650, Korea.|Department of Preventive Medicine, Korea University, Korea Project for Reducing Light Pollution Effects to Human and Ecosystem, Korea.
authors.forename: Seung-Chan
authors.initials: SC
authors.lastname: Jeong
authors.affiliation: Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology, P.O. Box 131, Cheongryang, Seoul, 130-650, Korea.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Cho
authors.affiliation: National Center for Efficacy evaluation for Respiratory disease product, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, 30 Baehak1-gil, Jeongeup, Jeollabuk-do, 53212, Republic of Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Song
authors.affiliation: Department of Preventive Medicine, Korea University, Korea Project for Reducing Light Pollution Effects to Human and Ecosystem, Korea.
authors.forename: Eunil
authors.initials: E
authors.lastname: Lee
authors.affiliation: Cellular and Molecular Toxicology Laboratory, Korea Institute of Science & Technology, P.O. Box 131, Cheongryang, Seoul, 130-650, Korea.|Department of Pharmacology and Toxicology, Human and Environmental Toxicology, Korea University of Science and Technology, Gajeong-Ro 217, Yuseong-gu, Daejeon, 305-350, Korea.
authors.forename: Jae-Chun
authors.initials: JC
authors.lastname: Ryu
mesh_terms: D000072283:A549 Cells; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D052638:Particulate Matter; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases
keywords: Cytokine; epidermal growth factor receptor (EGFR); erlotinib; mitogen-activated protein kinase (MAPK); particulate matter2.5(PM2.5)