title: World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung.
abstract: Exposure to World Trade Center (WTC) dust has been linked to respiratory disease in humans. In the present studies we developed a rodent model of WTC dust exposure to analyze lung oxidative stress and inflammation, with the goal of elucidating potential epigenetic mechanisms underlying these responses. Exposure of mice to WTC dust (20μg, i.t.) was associated with upregulation of heme oxygenase-1 and cyclooxygenase-2 within 3days, a response which persisted for at least 21days. Whereas matrix metalloproteinase was upregulated 7days post-WTC dust exposure, IL-6RA1 was increased at 21days; conversely, expression of mannose receptor, a scavenger receptor important in particle clearance, decreased. After WTC dust exposure, increases in methylation of histone H3 lysine K4 at 3days, lysine K27 at 7days and lysine K36, were observed in the lung, along with hypermethylation of Line-1 element at 21days. Alterations in pulmonary mechanics were also observed following WTC dust exposure. Thus, 3days post-exposure, lung resistance and tissue damping were decreased. In contrast at 21days, lung resistance, central airway resistance, tissue damping and tissue elastance were increased. These data demonstrate that WTC dust-induced inflammation and oxidative stress are associated with epigenetic modifications in the lung and altered pulmonary mechanics. These changes may contribute to the development of WTC dust pathologies.
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States. Electronic address: sunilva@pharmacy.rutgers.edu.
authors.forename: Vasanthi R
authors.initials: VR
authors.lastname: Sunil
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States.
authors.forename: Kinal N
authors.initials: KN
authors.lastname: Vayas
authors.affiliation: Department of Environmental and Occupational Health, Rutgers School of Public Health, Piscataway, NJ, United States.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Environmental and Occupational Health, Rutgers School of Public Health, Piscataway, NJ, United States.
authors.forename: Helmut
authors.initials: H
authors.lastname: Zarbl
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Massa
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gow
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Cervelli
authors.affiliation: Department of Environmental and Occupational Health, Rutgers School of Public Health, Piscataway, NJ, United States.
authors.forename: Howard
authors.initials: H
authors.lastname: Kipen
authors.affiliation: Department of Environmental and Occupational Health, Rutgers School of Public Health, Piscataway, NJ, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Laumbach
authors.affiliation: Department of Environmental and Occupational Health, Rutgers School of Public Health, Piscataway, NJ, United States.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lioy
authors.affiliation: Department of Environmental and Occupational Health, Rutgers School of Public Health, Piscataway, NJ, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laskin
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ, United States.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D004391:Dust; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008239:Lysine / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047851:September 11 Terrorist Attacks; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D004391:Dust; D006657:Histones; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases; D008239:Lysine
keywords: Epigenetics; Inflammation; Lung; Lung function; Oxidative stress; WTC dust