title: Effects of naphthoquinone on airway responsiveness in the presence or absence of antigen in mice.
abstract: We have recently demonstrated that naphthoquinone (NQ), one of extractable chemical compounds of diesel exhaust particles (DEP), enhances antigen-related airway inflammation with goblet cell hyperplasia in mice (Inoue et al. in Eur Respir J 209(2):259-267, 2007). Further, NQ has enhanced lung expressions of interleukin (IL)-4 and IL-5. However, the effects of NQ on other cardinal features of asthma have not been completely investigated. The aim of the present study was to evaluate the effects of NQ on airway responsiveness on the model. Vehicle, NQ, ovalbumin (OVA), or NQ + OVA was administered intratarcheally to ICR mice for 6 weeks. Twenty-four hours after the last instillation, lung histology, lung functions such as total respiratory system resistance (R) and Newtonian resistance (R (n)), and protein level of IL-13 and mRNA level for MUC5AC in the lung were examined. Repetitive exposure to NQ aggravated antigen-related lung inflammation. NQ alone enhanced R and R (n) as compared to vehicle without statistical significance. OVA alone or NQ plus OVA showed increases in R and R (n), which was prominent in NQ plus OVA (P < 0.05 vs. vehicle). Combined exposure to NQ and OVA elevated the levels of IL-13 and MUC5AC in the lung as compared with exposure to NQ or OVA alone. These results indicate that NQ can enhance airway hyperresponsiveness in the presence or absence of an antigen. Also, amplified lung expressions of IL-13 and MUC5AC might partly contribute to the deterioration of asthma features by NQ.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan, htakano@nies.go.jp.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
authors.forename: Shigeo
authors.initials: S
authors.lastname: Tomura
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Miho
authors.initials: M
authors.lastname: Sakurai
authors.forename: Daigo
authors.initials: D
authors.lastname: Sumi
authors.forename: Arthur K
authors.initials: AK
authors.lastname: Cho
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hiyoshi
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D018793:Interleukin-13 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics; D009285:Naphthoquinones / Q000633:toxicity*; D010047:Ovalbumin / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D001335:Vehicle Emissions
chemical_list: D000941:Antigens; D018793:Interleukin-13; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D009285:Naphthoquinones; D012333:RNA, Messenger; D001335:Vehicle Emissions; D010047:Ovalbumin