The Journal of Experimental Medicine
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Published 15 October 2001. doi:10.1084/jem.194.8.1021
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© The Rockefeller University Press, 0022-1007/2001/10/1021/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 8, October 15, 2001 1021-1032

Original Article

C-Rel Regulates Interleukin 12 P70 Expression in Cd8+ Dendritic Cells by Specifically Inducing p35 Gene Transcription

Raelene Grumonta, Hubertus Hochreina, Meredith O'Keeffea, Raffi Gugasyana, Christine Whitea, Irina Caminschia, Wendy Cooka, and Steve Gerondakisa

a The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria 3050, Australia
The Walter and Eliza Hall Institute of Medical Research, Post Office The Royal Melbourne Hospital, Victoria 3050, Australia.61-3-9347085261-3-93452542

gerondakis{at}wehi.edu.au

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)-{kappa}B 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-{kappa}B is controlled through both the p35 and p40 genes in a cell type–specific fashion.

Key Words: c-rel • IL-12 • dendritic cells • p35 gene • transcription

R. Grumont and H. Hochrein contributed equally to this work.

H. Hochrein's present address is Medical Microbiology, Department of Immunology and Hygiene, Technical University of Munich, Munich D-81675, Germany.

Abbreviations used in this paper: DC, dendritic cell; EMSA, electrophoretic mobility shift assay; NF, nuclear factor; SAC, Staphylococcus aureus.

© 2001 The Rockefeller University Press


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