| First Author | Lv S | Year | 2017 |
| Journal | Cell Death Differ | Volume | 24 |
| Issue | 3 | Pages | 492-499 |
| PubMed ID | 28009352 | Mgi Jnum | J:258647 |
| Mgi Id | MGI:6142427 | Doi | 10.1038/cdd.2016.148 |
| Citation | Lv S, et al. (2017) A negative feedback loop of ICER and NF-kappaB regulates TLR signaling in innate immune responses. Cell Death Differ 24(3):492-499 |
| abstractText | The NF-kappaB pathway has important roles in innate immune responses and its regulation is critical to maintain immune homeostasis. Here, we report a newly discovered feedback mechanism for the regulation of this pathway by TLR ligands in macrophages. Lipopolysaccharide (LPS) induced the expression of ICER via p38-mediated activation of CREB in macrophages. ICER, in turn, inhibited the transcriptional activity of NF-kappaB by direct interaction with the p65 subunit of NF-kappaB. Deficiency in ICER elevated binding of NF-kappaB to promoters of pro-inflammatory genes and their subsequent gene expression. Mice deficient in ICER were hypersensitive to LPS-induced endotoxic shock and showed propagated inflammation. Whereas ICER expression in ICER KO bone marrow transplanted mice rescued the ultra-inflammation phenotype, expression of a p65 binding-deficient ICER mutant failed to do so. Our results thus establish p38-CREB-ICER as key components of a negative feedback mechanism necessary to regulate TLR-driven inflammation. |
