title: Synergistic effect of bolus exposure to zinc oxide nanoparticles on bleomycin-induced secretion of pro-fibrotic cytokines without lasting fibrotic changes in murine lungs.
abstract: Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. wendyvvri@med.nagoya-u.ac.jp.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Occupational and Environmental Health, Tokyo University of Science, Noda 278-8510, Japan. gak@rs.tus.ac.jp.
authors.forename: Gaku
authors.initials: G
authors.lastname: Ichihara
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. hashinao@med.nagoya-u.ac.jp.
authors.forename: Naozumi
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. yhasega@med.nagoya-u.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Electrical and Electronic Engineering, Okayama University, Okayama 700-8530, Japan. hayashi.yasuhiko@ec.okayama-u.ac.jp.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. t-saeko@innov.mie-u.ac.jp.
authors.forename: Saeko
authors.initials: S
authors.lastname: Tada-Oikawa
authors.affiliation: Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. suzujohn@yahoo.co.jp.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. jie-chang@med.nagoya-u.ac.jp.
authors.forename: Jie
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. katomasa@med.nagoya-u.ac.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Immunology, Mie University School of Medicine, Tsu 514-8507, Japan. dalessac@clin.medic.mie-u.ac.jp.
authors.forename: Corina N
authors.initials: CN
authors.lastname: D'Alessandro-Gabazza
authors.affiliation: Department of Immunology, Mie University School of Medicine, Tsu 514-8507, Japan. gabazza@doc.medic.mie-u.ac.jp.
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
authors.affiliation: Graduate School of Regional Innovation Studies, Mie University, Tsu 514-8507, Japan. saho@gene.mie-u.ac.jp.
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015034:Zinc Oxide / Q000737:chemistry
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D053583:Interleukin-1beta; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D015034:Zinc Oxide