| First Author | Grumont R | Year | 2001 |
| Journal | J Exp Med | Volume | 194 |
| Issue | 8 | Pages | 1021-32 |
| PubMed ID | 11602633 | Mgi Jnum | J:72212 |
| Mgi Id | MGI:2152000 | Doi | 10.1084/jem.194.8.1021 |
| Citation | Grumont R, et al. (2001) c-Rel Regulates Interleukin 12 p70 Expression in CD8(+) Dendritic Cells by Specifically Inducing p35 Gene Transcription. J Exp Med 194(8):1021-32 |
| abstractText | Interleukin 12 (IL-12) is a 70-kD proinflammatory cytokine produced by antigen presenting cells that is essential for the induction of T helper type 1 development. It comprises 35-kD (p35) and 40-kD (p40) polypeptides encoded by separate genes that are induced by a range of stimuli that include lipopolysaccharide (LPS), DNA, and CD40 ligand. To date, the regulation of IL-12 expression at the transcriptional level has mainly been examined in macrophages and restricted almost exclusively to the p40 gene. Here we show that in CD8(+) dendritic cells, major producers of IL-12 p70, the Rel/nuclear factor (NF)-kappaB signaling pathway is necessary for the induction of IL-12 in response to microbial stimuli. In contrast to macrophages which require c-Rel for p40 transcription, in CD8(+) dendritic cells, the induced expression of p35 rather than p40 by inactivated Staphylococcus aureus, DNA, or LPS is c-Rel dependent and regulated directly by c-Rel complexes binding to the p35 promoter. This data establishes the IL-12 p35 gene as a new target of c-Rel and shows that the regulation of IL-12 p70 expression at the transcriptional level by Rel/NF-kappaB is controlled through both the p35 and p40 genes in a cell type-specific fashion. |
