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-κB subunit p50 (NF-κBp50). Finally, we demonstrated that LXR can associate with NF-κBp50 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-κBp50 and highlights its potential as a therapeutic target for chronic inflammatory diseases.
Original language | English |
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Pages (from-to) | 675-87 |
Journal | Innate Immunity |
Volume | 20 |
Issue number | 7 |
DOIs | |
Publication status | Published - 01 Oct 2014 |
Keywords
- Animals
- Bone Marrow Cells
- Cell Nucleus
- Colitis
- Cytokines
- Cytoplasm
- Inflammation
- Interleukin-12
- Liver X Receptors
- Mice
- Mice, Inbred BALB C
- NF-kappa B p50 Subunit
- Orphan Nuclear Receptors
- Protein Transport
- RNA, Messenger
- Journal Article
- Research Support, Non-U.S. Gov't