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Coxsackievirus B3 infection increases the tissue levels of BDE-99 in the mouse liver
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Infektionssjukdomar)
Livsmedelsverket. (Toxikologiska enheten)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. (Infektionssjukdomar)
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The flame retardant 2,2’,4,4’,5-penta-BDE (BDE-99) is accumulated in human tissues. The common human infection that is caused by coxsackievirus B3 (CVB3) changes the tissue distribution of BDE-99 in exposed mice. In this study we investigated whether CVB3 infection in mice causes dose-dependent changes in the tissue levels of radiolabelled 14C-BDE-99 and whether the tissue levels are associated with virus replication and gene expression of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1). Mice were infected with CVB3 or sham-inoculated on day 0, orally treated either with 200 µg 14C-BDE-99/kg bw or 20 mg 14C-BDE-99/kg bw on day 1 and euthanized on day 3. Virus levels and gene expressions were measured using real-time polymerase chain reaction (RT-PCR) and tissue concentrations of 14C-BDE-99 were measured by liquid scintillation counting. A dose-dependent uptake of BDE-99 was observed in both the liver and serum. The BDE-99 level in the liver was further increased at both doses by the CVB3 infection. In addition, at the higher dose, BDE-99 increased the virus amount in the liver, whereas the infection-induced expression of MCP-1 was greatly decreased at the higher BDE-99 dose. In conclusion, BDE-99 dose-dependently increased the levels in the liver and serum and the levels in the liver were further increased by the infection and associated with an increase in virus levels in this organ. However, the infection-induced change in BDE-99 levels was not noted in serum, a fact that may complicate the risk assessment in subclinical and clinically infected individuals.

Keyword [en]
PBDE; coxsackievirus B3; tissue distribution; virus levels; MCP-1
Research subject
Medical Virology; Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-108847OAI: oai:DiVA.org:uu-108847DiVA: diva2:240974
Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2010-01-14
In thesis
1. Coxsackievirus B3 Infection and Host Defence Responses Change the Metabolism of PBDE
Open this publication in new window or tab >>Coxsackievirus B3 Infection and Host Defence Responses Change the Metabolism of PBDE
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It has been suggested that the rising amounts of chemicals in the environment may affect host resistance and increase susceptibility to infections. Studies have also shown that infections can change the toxicity of pollutants. The aim of this thesis was to study interactions between environmental pollutant exposure in terms of polybrominated diphenyl ethers (PBDE) and a common human coxsackievirus B3 (CVB3) infection adapted to Balb/c mice. The studies focused on virus levels, cytokines, metabolising cytochrome P450 (CYP) enzymes and tissue distribution of PBDE.

A novel finding was an organ-specific effect of CVB3 infection on the metabolising capacity of PBDE. The PBDE metabolising enzyme CYP2B10 was down-regulated by the CVB3 infection in the liver, up-regulated in the lungs, but not affected in the pancreas. Accordingly, CVB3 infection increased the concentration of PBDE in the livers of infected mice. However, serum levels of PBDE were not affected by the infection, indicating that serum does not reflect the actual organ exposure of PBDE in infected individuals. The change in metabolising capacity was likely mediated by infection-induced cytokines and associated effects on the nuclear factor-κB (NF-κB) pathway.

PBDE drastically decreased serum levels of several cytokines and chemokines, an event that may create a slot for viruses to replicate. Accordingly, some results show that infected mice exposed to a high dose of PBDE had higher virus levels than mice exposed to a low dose.

In conclusion, infected individuals showed organ-specific changes in metabolism and tissue levels of PBDE, which potentially could change the toxicity of PBDE. PBDE also seems to affect the fate of the infection. NF-κB activated pathways may mediate one possible mechanism underlying these effects. Thus, further investigations of this pathway are warranted. In addition, future studies should address how PBDE exposure affects viral replication.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 73 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 487
Keyword
Coxsackievirus, environmental pollutants, PBDE, cytokines, chemokines, metabolism, infection, tissue distribution, toxicology, virology, immunology
National Category
Pharmacology and Toxicology Microbiology in the medical area
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-108849 (URN)978-91-554-7619-9 (ISBN)
Public defence
2009-11-13, Universitetshuset, sal IV, Universitetsparken, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2009-10-27 Created: 2009-09-30 Last updated: 2009-10-27Bibliographically approved

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