Peer-Reviewed Journal Details
Mandatory Fields
Canavan, M;McCarthy, C;Ben Larbi, N;Dowling, JK;Collins, L;O'Sullivan, F;Hurley, G;Murphy, C;Quinlan, A;Moloney, G;Darby, T;MacSharry, J;Kagechika, H;Moynagh, P;Melgar, S;Loscher, CE
2014
October
Journal of Innate Immunity
Activation of liver X receptor suppresses the production of the IL-12 family of cytokines by blocking nuclear translocation of NF-kappa Bp50
Published
8 ()
Optional Fields
NF-KAPPA-B INFLAMMATORY-BOWEL-DISEASE DENDRITIC CELLS PPAR-GAMMA C-REL INDUCTION TRANSCRIPTION MACROPHAGES EXPRESSION HOMEOSTASIS
20
675
687
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-kappa B subunit p50 (NF-kappa Bp50). Finally, we demonstrated that LXR can associate with NF-kappa Bp50 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-kappa Bp50 and highlights its potential as a therapeutic target for chronic inflammatory diseases.
LONDON
1753-4259
10.1177/1753425913501915
Grant Details