The effects of BDE-99 on the gene expression of MCP-1, IFN-γ, NF-κB and the metabolising enzyme CYP3A, during coxsackievirus B3 infection
(English)Manuscript (preprint) (Other academic)
It has been shown that coxsackievirus B3 (CVB3), a common virus with a similar disease development in mice and humans, affects CYP-enzymes and the metabolism of environmental pollutants, such as 2,2’,4,4’,5-penta-BDE (BDE-99). The transcription factor nuclear factor-κB (NF-κB) regulates several genes, including the proinflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) and the cytokine interferon-γ (IFN-γ). These immune mediators are produced during infection and are involved in the antiviral defence as well as in the regulation of genes for CYP enzyme synthesis. The aim of the study was to investigate how interactions between infection and concomitant BDE-99 exposure affects virus levels, gene expression of MCP-1, IFN-γ, NF-κB, CYP3A11 and subsequent CYP3A enzyme activity. Female Balb/c mice were infected with CVB3 on day 0, orally exposed to BDE-99 (20 mg/kg bw) on day 1 and put to death on day 3. The gene expression of MCP-1, IFN-γ, NF-κB, CYP3A11 and the levels of CVB3 were measured with RT-PCR in the liver. The present study suggests that CYP3A is involved in the metabolism of PBDE. In general, infection decreased the expression and CYP3A enzyme activity, increased the gene expression of MCP-1 and NF-κB, but did not affect gene expression of IFN-γ. BDE-99 exposure in non-infected mice increased CYP3A enzyme activity but not the gene expression of MCP-1, IFN-γ, NF-κB and CYP3A11. Although, CVB3 induced gene expression of NF-κB and of MCP-1, as well as concomitant down-regulation of CYP3A11 gene expression and enzyme activity, no clear interaction effects had yet developed at this early stage of disease.
Immunology in the medical area
IdentifiersURN: urn:nbn:se:uu:diva-108848OAI: oai:DiVA.org:uu-108848DiVA: diva2:240983