title: Involvement of EGF receptor signaling and NLRP12 inflammasome in fine particulate matter-induced lung inflammation in mice.
abstract: Epidemiological studies have shown that exposure to ambient fine particulate matter (PM2.5) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM2.5exposure. However, the mechanisms underlying PM2.5-induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM2.5-induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM2.5suspension (4.0 mg/kg b.w.) for 5 consecutive days, respectively. Bronchoalveolar lavage (BAL) was conducted and BAL fluid (BALF) was collected. The levels of reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), epidermal growth factor (EGF), CXCL1, interleukin (IL)-1β, and IL-18 in BALF were determined using ELISA. mRNA levels of IL-6, IL-1β, IL-18, CXCL1, IL-10, NLRP3, Caspase-1, and NLRP12 in lung tissues were determined by RT-PCR. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) in lung tissues were examined using immunohistochemical staining and Western blotting, respectively. Protein levels of Caspase-1, NLRP3, NF-κB-p52/p100, and NF-κB-p65 in bronchial epithelium were examined using immunohistochemical staining. It was shown that PM2.5exposure induced lung inflammation. Levels of total protein, ROS, iNOS, EGF, and CXCL1 and cell number in the BALF of mice exposed to PM2.5were markedly elevated relative to the control. mRNA levels of CXCL1, IL-1β, and IL-18 in lung tissues of PM2.5-exposed mice were increased in comparison with the control. However, level of NLRP12 mRNA in lung tissues of PM2.5-exposed mice was reduced. Phospho-EGFR (Tyr1068) and phospho-Akt (Thr308) levels in the lungs of PM2.5-instilled mice were higher than those in the lungs of the control. The protein levels of NF-κB-p52/p100 and NF-κB-p65 in bronchial epithelium of PM2.5-exposed mice were also increased compared with the control. This study suggests that EGF-EGFR-Akt-NF-κB signaling and NLRP12 inflammasome may be associated with PM2.5-induced lung inflammation in mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1121-1134, 2017.
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Jin
authors.affiliation: School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China.|Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Immunology and Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Zhengzhou Center for Disease Control and Prevention, Zhengzhou, Henan, China.
authors.forename: Guoyin
authors.initials: G
authors.lastname: Ge
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ba
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Gao
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Chi
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Huiyun
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Pulmonary Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Feng
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D058847:Inflammasomes / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D000393:Air Pollutants; D058847:Inflammasomes; D053583:Interleukin-1beta; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; C553199:NLRP12 protein, mouse; D052638:Particulate Matter; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: NF-κB; epidermal growth factor receptor; fine particulate matter; inflammasome; lung inflammation