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

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

Validated

Altmetric: 1 ()

Liver X receptor dendritic cells interleukin-12 NF-kappa B 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.

10.1177/1753425913501915