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    Activation of liver X receptor suppresses the production of the IL-12 family of cytokines by blocking nuclear translocation of NF-kBp50


    Canavan, Mary and McCarthy, Ciara and Ben Larbi, Nadia and Dowling, Jennifer and Collins, Laura and O'Sullivan, Finbarr and Hurley, Grainne and Murphy, Carola and Quinlan, Aoife and Moloney, Gerry and Darby, Trevor and MacSharry, John and Kagechika, Hiroyuki and Moynagh, Paul N. and Melgar, Silvia and Loscher, Christine E. (2013) Activation of liver X receptor suppresses the production of the IL-12 family of cytokines by blocking nuclear translocation of NF-kBp50. Innate Immunity. ISSN 1753-4259

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    Abstract

    There is now convincing evidence that liver X receptor (LXR) is an important modulator of the inflammatory response; however, its mechanism of action remains unclear. This study aimed to examine the effect of LXR on the IL-12 family of cytokines and examined the mechanism by which LXR exerted this effect. We first demonstrated that activation of murine-derived dendritic cells (DC) with a specific agonist to LXR enhanced expression of LXR following activation with LPS, suggesting a role in inflammation. Furthermore, we showed LXR expression to be increased in vivo in dextrane sulphate sodium-induced colitis. LXR activation also suppressed production of IL-12p40, IL-12p70, IL-27 and IL-23 in murine-derived DC following stimulation with LPS, and specifically targeted the p35, p40 and EBI3 subunits of the IL-12 cytokine family, which are under the control of the NF-kB subunit p50 (NF-kBp50). Finally, we demonstrated that LXR can associate with NF-kBp50 in DC and that LXR activation prevents translocation of the p50 subunit into the nucleus. In summary, our study indicates that LXR can specifically suppress the IL-12 family of cytokines though its association with NF-kBp50 and highlights its potential as a therapeutic target for chronic inflammatory diseases.

    Item Type: Article
    Keywords: Liver X receptor; dendritic cells; interleukin-12;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 4953
    Identification Number: http://10.1177/1753425913501915
    Depositing User: Professor Paul Moynagh
    Date Deposited: 13 May 2014 15:49
    Journal or Publication Title: Innate Immunity
    Publisher: SAGE Publications (UK and US)
    Refereed: Yes
    URI:

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