| First Author | Lai TY | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 9 | Pages | e73153 |
| PubMed ID | 24023826 | Mgi Jnum | J:206401 |
| Mgi Id | MGI:5550192 | Doi | 10.1371/journal.pone.0073153 |
| Citation | Lai TY, et al. (2013) Transcription of Tnfaip3 is regulated by NF-kappaB and p38 via C/EBPbeta in activated macrophages. PLoS One 8(9):e73153 |
| abstractText | Macrophages play a pivotal role in the immune system through recognition and elimination of microbial pathogens. Toll-like receptors (TLRs) on macrophages interact with microbial substances and initiate signal transduction through intracellular adapters. TLR4, which recognizes the lipopolysaccharides (LPS) on Gram-positive and Gram-negative bacteria, triggers downstream signaling mediators and eventually activates IkappaB kinase (IKK) complex and mitogen-activated protein kinases (MAPKs) such as p38. Previous reports revealed that, in addition to NF-kappaB, a core transcription factor of the innate immune response, the induction of some LPS-induced genes in macrophages required another transcription factor whose activity depends on p38. However, these additional transcription factors remain to be identified. In order to identify p38-activated transcription factors that cooperate with NF-kappaB in response to LPS stimulation, microarrays were used to identify genes regulated by both NF-kappaB and p38 using wild-type, IKK-depleted, and p38 inhibitor-treated mouse bone marrow-derived macrophages (BMDMs). In silico analysis of transcription factor binding sites was used to predict the potential synergistic transcription factors from the co-expressed genes. Among these genes, NF-kappaB and C/EBPbeta, a p38 downstream transcription factor, were predicted to co-regulate genes in LPS-stimulated BMDMs. Based on the subsequent results of a chromatin immunoprecipitation assay and TNFAIP3 expression in C/EBPbeta-ablated macrophages, we demonstrated that Tnfaip3 is regulated by both NF-kappaB and p38-dependent C/EBPbeta. These results identify a novel regulatory mechanism in TLR4-mediated innate immunity. |
