Publications & Reports

c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription.

R Grumont, H Hochrein, M O'Keeffe, R Gugasyan, C White, I Caminschi, W Cook, S Gerondakis
The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria 3050, Australia.

Abstract

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.

Publication

  • Journal: The Journal of Experimental Medicine
  • Published: 15/10/2001
  • Volume: 194
  • Issue: 8
  • Pagination: 1021-1032

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