| First Author | Yamamoto M | Year | 2007 |
| Journal | J Exp Med | Volume | 204 |
| Issue | 9 | Pages | 2233-9 |
| PubMed ID | 17724128 | Mgi Jnum | J:126085 |
| Mgi Id | MGI:3760491 | Doi | 10.1084/jem.20070183 |
| Citation | Yamamoto M, et al. (2007) Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency. J Exp Med 204(9):2233-9 |
| abstractText | Toll-like receptors (TLRs) recognize a variety of microbial components and mediate downstream signal transduction pathways that culminate in the activation of nuclear factor kappaB (NF-kappaB) and mitogen-activated protein (MAP) kinases. Trib1 is reportedly involved in the regulation of NF-kappaB and MAP kinases, as well as gene expression in vitro. To clarify the physiological function of Trib1 in TLR-mediated responses, we generated Trib1-deficient mice by gene targeting. Microarray analysis showed that Trib1-deficient macrophages exhibited a dysregulated expression pattern of lipopolysaccharide-inducible genes, whereas TLR-mediated activation of MAP kinases and NF-kappaB was normal. Trib1 was found to associate with NF-IL6 (also known as CCAAT/enhancer-binding protein beta). NF-IL6-deficient cells showed opposite phenotypes to those in Trib1-deficient cells in terms of TLR-mediated responses. Moreover, overexpression of Trib1 inhibited NF-IL6-dependent gene expression by down-regulating NF-IL6 protein expression. In contrast, Trib1-deficient cells exhibited augmented NF-IL6 DNA-binding activities with increased amounts of NF-IL6 proteins. These results demonstrate that Trib1 is a negative regulator of NF-IL6 protein expression and modulates NF-IL6-dependent gene expression in TLR-mediated signaling. |
