title: Low-dose benzo[a]pyrene aggravates allergic airway inflammation in mice.
abstract: Benzo[a]pyrene (BaP) reportedly has mutagenic and adjuvant activities. We aimed to determine the effects of low-dose BaP administration on allergic airway inflammation and mediastinal lymph node (MLN) cell activation/proliferation in mice. Male C3H/HeJ mice were intratracheally administered ovalbumin (OVA) every 2 weeks and/or BaP (0, 0.05, 1 and 20 pmol per animal per week) once per week for 6 weeks. The cellular profile of bronchoalveolar lavage (BAL) fluid, histological changes, inflammatory cytokines/chemokines in the lungs, OVA-specific immunoglobulin (Ig) in serum and MLN cell activation/proliferation were examined. BaP administration of 20 pmol with OVA enhanced neutrophil and macrophage accumulation in the lungs. Compared with OVA administration, BaP administration with OVA tended to enhance pulmonary eosinophilia and goblet cell hyperplasia. Furthermore, it increased the levels of interleukin (IL)-5, IL-13, IL-33, monocyte chemoattractant protein-1 and eotaxin in the lungs, and OVA-specific IgG1 in serum, although not dose-dependently. Compared with the vehicle group, IL-6 and tumor necrosis factor-alpha levels were higher in the OVA + 1 pmol BaP group and IL-12 production was higher in the OVA + 20 pmol BaP group. Ex vivo studies showed that co-exposure to OVA and BaP activated the MHC class II and CD86 expression in MLN cells. Exposure to BaP with OVA increased IL-4, IL-5 and interferon gamma levels in culture supernatants of OVA-re-stimulated MLN cells. In conclusion, low-dose BaP can, at least in part, enhance allergic airway inflammation by facilitating Th2 responses and activating MLN cells; a high BaP dose may contribute to activating both Th1 and Th2 responses. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, 305-8506, Japan. yanagisawa.rie@nies.go.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, 305-8506, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, 305-8506, Japan.
authors.forename: Tin-Tin
authors.initials: TT
authors.lastname: Win-Shwe
authors.affiliation: Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, 870-1201, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
authors.affiliation: Graduate School of Engineering, Kyoto University, Kyoto-Daigaku-Katsura, Nishikyo-ku, Kyoto, 615-8530, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D007074:Immunoglobulin G / Q000097:blood; D007378:Interleukins / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D004785:Environmental Pollutants; D007074:Immunoglobulin G; D007378:Interleukins; D001564:Benzo(a)pyrene; D010047:Ovalbumin
keywords: Th2 responses; allergic airway inflammation; benzo[a]pyrene; diesel exhaust particles; polycyclic aromatic hydrocarbons