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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.

SUBMITTER: Watanabe W

PROVIDER: S-EPMC3866880 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Perinatal exposure to insecticide methamidophos suppressed production of proinflammatory cytokines responding to virus infection in lung tissues in mice.

Watanabe Wataru W Yoshida Hiroki H Hirose Akihiko A Akashi Toshi T Takeshita Tomomi T Kuroki Nao N Shibata Asami A Hongo Satoko S Hashiguchi Seiko S Konno Katsuhiko K Kurokawa Masahiko M

BioMed research international 20131203

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 ...[more]

PMID: 24369005

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Project description:BackgroundGout is considered one of the most painful acute conditions caused by deposition of monosodium urate (MSU) crystals within joints. Recent studies have shown that interleukin (IL)-1β is a key inflammatory mediator in acute gouty arthritis (GA), and its level is regulated by microRNAs (miRNAs). However, the molecular mechanisms of the regulation remain unclear.MethodsA miRNA microarray was used to analyze the miRNA expression profiles in peripheral white blood cells (WBCs) of patients with GA. THP-1 cells were transfected with miRNA mimics, stimulated by MSU crystals, and then subjected to quantitative real-time polymerase chain reaction or Western blot analysis. Levels of IL-1β, IL-8, and tumor necrosis factor (TNF)-α in culture supernatants of THP-1 cells were measured by enzyme-linked immunosorbent assay. A luciferase reporter assay was conducted to confirm the interaction of miRNA and IL-1β 3'-untranslated regions (UTRs).ResultsCombining bioinformatics and miRNA expression profiles, we found five miRNAs (hsa-miR-30c-1-3p, hsa-miR-488-3p, hsa-miR-550a-3p, hsa-miR-663a, and hsa-miR-920) that possibly target IL-1β. Then, we demonstrated that miR-488 and miR-920 were significantly decreased in the WBCs of patients with GA and that MSU crystals could inhibit expression of miR-488 and miR-920. Upregulation of miR-488 and miR-920 could suppress MSU-induced IL-1β protein expression in THP-1 cells, but no significant difference in IL-1β messenger RNA levels was observed. Moreover, we found that miR-488 and miR-920 could directly target the 3'-UTR of IL-1β. Overexpression of miR-488 and miR-920 could significantly inhibit the gene and protein expression of IL-8 and TNF-α in MSU-induced THP-1 cells.ConclusionsThis study demonstrates the roles of miR-488 and miR-920 in regulating the production of proinflammatory cytokines in the pathogenesis of GA. These findings suggest that miR-488 and miR-920 could serve as potential therapeutic targets in the treatment of GA.

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Perinatal exposure to insecticide methamidophos suppressed production of proinflammatory cytokines responding to virus infection in lung tissues in mice.

Publications

Perinatal exposure to insecticide methamidophos suppressed production of proinflammatory cytokines responding to virus infection in lung tissues in mice.

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