| First Author | Lee HH | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 24921 | PubMed ID | 27118681 |
| Mgi Jnum | J:253796 | Mgi Id | MGI:6102389 |
| Doi | 10.1038/srep24921 | Citation | Lee HH, et al. (2016) LPS-induced NFkappaB enhanceosome requires TonEBP/NFAT5 without DNA binding. Sci Rep 6:24921 |
| abstractText | NFkappaB is a central mediator of inflammation. Present inhibitors of NFkappaB are mostly based on inhibition of essential machinery such as proteasome and protein kinases, or activation of nuclear receptors; as such, they are of limited therapeutic use due to severe toxicity. Here we report an LPS-induced NFkappaB enhanceosome in which TonEBP is required for the recruitment of p300. Increased expression of TonEBP enhances the NFkappaB activity and reduced TonEBP expression lowers it. Recombinant TonEBP molecules incapable of recruiting p300 do not stimulate NFkappaB. Myeloid-specific deletion of TonEBP results in milder inflammation and sepsis. We discover that a natural small molecule cerulenin specifically disrupts the enhanceosome without affecting the activation of NFkappaB itself. Cerulenin suppresses the pro-inflammatory activation of macrophages and sepsis without detectable toxicity. Thus, the NFkappaB enhanceosome offers a promising target for useful anti-inflammatory agents. |
