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Polybrominated diphenyl ether exposure suppresses cytokines important in the defence to coxsackievirus B3 infection in mice
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 Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology. (blomberg)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. (friman)
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2009 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 184, no 2, 107-13 p.Article in journal (Refereed) Published
Abstract [en]

Environmental pollutants can adversely affect the immune system. The host defence during infection depends on cytokine signalling and proper function of immune cells. However, no studies have addressed how polybrominated diphenyl ethers (PBDEs) affect cytokine responses. We investigated the combined effects in Balb/c mice of human coxsackievirus B3 (CVB3) infection and exposure to PBDEs (BDE-99 or Bromkal mixture) on 21 serum cytokines. The mice were infected (i.p.) on day 0, orally treated with BDE-99 or Bromkal on day 1 (20mg/kg bw) and put to death on day 3. CVB3 was quantitatively measured in the liver and pancreas by RT-PCR. The Luminex 200 multi-analyte system was used for cytokine analysis. High numbers of viral copies were found in the liver and pancreas. Infection increased TNF-alpha, IL-6, MCP-1, IL-12p40, KC and RANTES levels. Notably, PBDE-exposure resulted in a marked decrease, or even lack, of IL-13, MIP-1beta, RANTES, IFN-gamma and KC levels in non-infected mice. However, the effects of PBDE-exposure on cytokines did not affect viral replication during early CVB3 infection. In conclusion, PBDEs causes a selective block in immune signalling pathways but the consequences of this need to be further studied in different host resistance models of infection.

Place, publisher, year, edition, pages
2009. Vol. 184, no 2, 107-13 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-102542DOI: 10.1016/j.toxlet.2008.10.021ISI: 000263219900006PubMedID: 19022362OAI: oai:DiVA.org:uu-102542DiVA: diva2:216330
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)
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Supervisors
Available from: 2009-10-27 Created: 2009-09-30 Last updated: 2009-10-27Bibliographically approved

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