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Coxsackievirus B3 infection and PBDE exposure causes organ-specific effects on CYP-gene expression in the mouse
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. (friman)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. (friman)
Livsmedelsverket.
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2007 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 242, no 1-3, 91-99 p.Article in journal (Refereed) Published
Abstract [en]

Common viral infections have been shown to change the tissue distribution of xenobiotics, including polybrominated diphenyl ethers (PBDEs). In previous studies, it has been shown that CYP2B gene expression is induced after PBDE exposure whereas coxsackievirus B3 (CBV3) infection suppresses the expression of CYP-gene expression in the liver. In the present study, CVB3 adapted to Balb/c mice was used to study the combined effects of infection and exposure to pure BDE-99 or the commercial mixture Bromkal on CYP1A1 and CYP2B expression in the lungs and pancreas on day 3 of the infection. The quantitative gene expression of virus, CYP1A1 and CYP2B was measured by real-time polymerase chain reaction (RT-PCR). PBDE exposure in the non-infected mice tended to increase CYP2B expression in the lungs but not in the pancreas. Infection in both non-exposed and PBDE-exposed mice increased CYP2B expression in the lungs but was non-detectable in the pancreas. In the non-infected mice PBDE exposure left the CYP1A1 expression unaltered in both the lungs and pancreas. Infection in both non-exposed and PBDE-exposed mice tended to decrease the gene expression of CYP1A1 in the lungs but to induce it in the pancreas. A correlation between the amount of virus and the gene expression of CYP2B was found in the lungs. However, no effects of PBDE on virus replication were observed in any organ. In conclusion, viral infection affects CYP-gene expression differently in the pancreas and lungs whereas PBDE-induced effects were not obvious. The organ-specific change in gene expression could explain a changed tissue distribution of xenobiotics during infection.

Place, publisher, year, edition, pages
2007. Vol. 242, no 1-3, 91-99 p.
Keyword [en]
Pancreas, Lung, PBDE, CYP1A1, CYP2B, Coxsackievirus B3
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-102548DOI: 10.1016/j.tox.2007.09.013ISI: 000251699900011PubMedID: 17964053OAI: oai:DiVA.org:uu-102548DiVA: diva2:216336
Available from: 2009-05-07 Created: 2009-05-07 Last updated: 2017-12-13Bibliographically approved
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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