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PLoS One. 2012;7(9):e45706. doi: 10.1371/journal.pone.0045706. Epub 2012 Sep 25.

IL-27-induced gene expression is downregulated in HIV-infected subjects.

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1
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.

Abstract

OBJECTIVE:

To characterize the effect of HIV infection on IL-27-induced gene expression.

DESIGN:

During HIV infection, cytokine expression and function become deregulated. IL-27 is an important modulator of inflammatory responses. Interestingly, IL-27 can inhibit HIV replication in T cells and monocytes, implicating IL-27 as a potential adjunct to anti-viral treatment. Our previous work demonstrated that circulating HIV may suppress IL-27 expression, therefore, this study, in continuation of our previous work, aimed to understand how HIV affects expression levels of the IL-27 receptor and downstream functions of IL-27.

METHODS:

Peripheral blood mononuclear cells (PBMC) were isolated from whole blood of HIV negative and HIV positive (viremic) individuals to assess IL-27-induced gene expression by flow cytometry and ELISA. PBMC were also processed for monocyte enrichment to assess IL-27 receptor expression by flow cytometry and real-time PCR.

RESULTS:

Expression of the IL-27 receptor subunit, gp130, was upregulated in response to IL-27 in HIV negative individuals, however, in HIV positive individuals, this IL-27 response was diminished. Furthermore, we observed downregulation of IL-27-induced IL-6, TNF-α, and IL-10 expression in HIV positive subjects.

CONCLUSION:

In HIV infection, IL-27-induced gene expression was impaired, indicating HIV-mediated dysregulation of IL-27 functions occurs during HIV infection. This study provides evidence for new viral pathogenic mechanisms contributing to the widespread impairment of immune responses observed in HIV pathogenesis.

PMID:
23049843
PMCID:
PMC3458084
DOI:
10.1371/journal.pone.0045706
[Indexed for MEDLINE]
Free PMC Article
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