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    Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-jB activity


    Siednienko, Jackub and Nowak, Joanna and Moynagh, Paul N. and Gorczyca, Wojciech A. (2011) Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-jB activity. Cytokine, 54. pp. 282-288. ISSN 1043-4666

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    Abstract

    Interleukin 6 (IL-6) and nitric oxide (NO) are important mediators of the inflammatory response. We report that in human peripheral blood mononuclear cells (PBMCs), NO exerts a biphasic effect on the expression of IL-6. Using sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO) as NO-donating compounds, we observed that both mRNA and protein levels of IL-6 increased at lower (610 lM) and decreased at higher (>100 lM) concentrations of NO donors. Changes in the expression of IL-6 correlated with changes in the activity of NF-jB, which increased at lower and decreased at higher concentrations of both NO donors as shown by the electrophoretic mobility shift assay (EMSA). The effects of NO on NF-jB activity were cGMP-dependent because they were reversed in the presence of ODQ, the inhibitor of soluble guanylyl cyclase (sGC), and KT5823, the inhibitor of cGMP-dependent protein kinase (PKG). Moreover, the membrane permeable analog of cGMP (8-Br-cGMP) mimicked the effect of the NO donors. These observations show that NO, depending on its concentration, may act in human PBMCs as a stimulator of IL-6 expression involving the sGC/cGMP/PKG pathway.

    Item Type: Article
    Additional Information: The definitive version of this article is available at doi:10.1016/j.cyto.2011.02.015
    Keywords: IL-6; NF-jB; Nitric oxide; cGMP; PBMC; Institute of Immunology; National University of Ireland Maynooth;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 4279
    Depositing User: Professor Paul Moynagh
    Date Deposited: 27 Mar 2013 17:17
    Journal or Publication Title: Cytokine
    Publisher: Elsevier
    Refereed: Yes
    URI:

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