title: Expression levels of neuroimmune biomarkers in hypothalamus of allergic mice after phthalate exposure.
abstract: Previously, we demonstrated that maternal exposure to phthalates enhances atopic dermatitis in male mouse offspring. However, whether phthalate exposure affects neuroimmune biomarkers in allergic mice has not yet been studied. Di-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP) are environmental chemicals that are commonly used as plasticizers. This study was designed to investigate the expression levels of neuroimmune biomarkers in the hypothalamus of a murine model of allergic asthma after phthalate exposure throughout juvenility until adulthood. Six-week-old C3H/HeJ Jcl male mice were treated with DEHP or DINP (0, 0.02, 0.4 or 8 nmol per body per week) and ovalbumin (OVA; 1 µg per body per 2 weeks) for 7 weeks intratracheally. On the day after the completion of the phthalate and OVA treatment, the hypothalamus from each mouse was collected, and the mRNA expression levels of neuroimmune biomarkers were examined using a real-time RT-PCR analysis. The mRNA expression levels of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, the chemokine CCL3, the transcription factor nuclear factor (NF)-κB, the oxidative stress marker heme-oxygenase (HO)1, a nerve growth factor, and the microglia marker Iba1 were remarkably up-regulated in the hypothalami of mice treated with 8 nmol of DEHP in the presence of the allergen. However, no significant changes were observed, except for reductions in the TNF-α and CCL2 mRNA levels, in mice exposed to DINP combined with the allergen. This study is the first report to show that high-dose DEHP exposure throughout juvenility until adulthood may induce neuroinflammation by modulating neuroimmune biomarkers in the hypothalami of allergic mice.
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan. tin.tin.win.shwe@nies.go.jp
authors.forename: Tin-Tin
authors.initials: TT
authors.lastname: Win-Shwe
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nitta
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
mesh_terms: D000485:Allergens / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism*; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020078:Neurogenic Inflammation / Q000139:chemically induced / Q000473:pathology*; D010047:Ovalbumin / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D010795:Phthalic Acids / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000485:Allergens; D015415:Biomarkers; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D053583:Interleukin-1beta; D008565:Membrane Proteins; D016328:NF-kappa B; D010795:Phthalic Acids; D010968:Plasticizers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C032279:phthalic acid; D010047:Ovalbumin; D004051:Diethylhexyl Phthalate; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse