title: Perinatal exposure to insecticide methamidophos suppressed production of proinflammatory cytokines responding to virus infection in lung tissues in mice.
abstract: Methamidophos, a representative organophosphate insecticide, is regulated because of its severe neurotoxicity, but it is suspected of contaminating agricultural foods in many countries due to illicit use. To reveal unknown effects of methamidophos on human health, we evaluated the developmental immunotoxicity of methamidophos using a respiratory syncytial virus (RSV) infection mouse model. Pregnant mice were exposed to methamidophos (10 or 20 ppm) in their drinking water from gestation day 10 to weaning on postnatal day 21. Offsprings born to these dams were intranasally infected with RSV. The levels of interleukin-6 (IL-6) and interferon-gamma in the bronchoalveolar lavage fluids after infection were significantly decreased in offspring mice exposed to methamidophos. Treatment with methamidophos did not affect the pulmonary viral titers but suppressed moderately the inflammation of lung tissues of RSV-infected offspring, histopathologically. DNA microarray analysis revealed that gene expression of the cytokines in the lungs of offspring mice exposed to 20 ppm of methamidophos was apparently suppressed compared with the control. Methamidophos did not suppress IL-6 production in RSV-infected J774.1 cell cultures. Thus, exposure of the mother to methamidophos during pregnancy and nursing was suggested to cause an irregular immune response in the lung tissues in the offspring mice.
authors.affiliation: Department of Microbiology, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Watanabe
authors.affiliation: Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hirose
authors.affiliation: Department of Microbiology and Infectious Diseases, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Akashi
authors.affiliation: Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Takeshita
authors.affiliation: Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Kuroki
authors.affiliation: Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Hongo
authors.affiliation: Department of Microbiology, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Hashiguchi
authors.affiliation: Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Konno
authors.affiliation: Department of Biochemistry, Graduate School of Clinical Pharmacy, Kyushu University of Health and Welfare, Yoshino 1714-1, Nobeoka, Miyazaki 882-8508, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurokawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007306:Insecticides / Q000633:toxicity*; D007371:Interferon-gamma / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D011247:Pregnancy; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000472:pathogenicity
chemical_list: D007306:Insecticides; D015850:Interleukin-6; D009946:Organothiophosphorus Compounds; D007371:Interferon-gamma; C014655:methamidophos