| First Author | Wang J | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 11 | Pages | 6777-88 |
| PubMed ID | 17513725 | Mgi Jnum | J:147847 |
| Mgi Id | MGI:3842282 | Doi | 10.4049/jimmunol.178.11.6777 |
| Citation | Wang J, et al. (2007) Distinct roles of different NF-kappa B subunits in regulating inflammatory and T cell stimulatory gene expression in dendritic cells. J Immunol 178(11):6777-88 |
| abstractText | TLRs play a critical role in inducing inflammatory and immune responses against microbial agents. In this study, we have investigated the role of NF-kappaB transcription factors in regulating TLR-induced gene expression in dendritic cells, a key APC type. The p50 and cRel NF-kappaB subunits were found to be crucial for regulating genes important for dendritic cell-induced T cell responses (e.g., CD40, IL-12, and IL-18) but not for genes encoding inflammatory cytokines (e.g., TNF-alpha, IL-1alpha, and IL-6). In striking contrast, the RelA subunit was crucial for expression of inflammatory cytokine genes but not T cell stimulatory genes. These novel findings reveal a fundamentally important difference in biological function of genes regulated by different NF-kappaB subunits. Focusing on RelA target gene specificity mechanisms, we investigated whether the kappaB site and/or the unique composition of RelA played the most crucial role. Surprisingly, studies of IL-6 expression showed that the kappaB site is not a primary determinant of RelA target gene specificity. Instead, a major specificity mechanism is the unique ability of RelA to interact with the transcriptional coactivator CREB-binding protein, a function not shared with the closely related cRel subunit. Together, our findings indicate novel and critically important overall roles of NF-kappaB in TLR-induced gene expression that are mediated by unique functions of distinct subunits. |
