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Induction of the TNF-alpha promoter in the murine dendritic cell line 18 and the murine mast cell line CPII is differently regulated.

E E Preischl, G G Pendl, A Elbe, E Serfling, N E Harrer, G Stingl and T Baumruker
J Immunol September 15, 1996, 157 (6) 2645-2653;
E E Preischl
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G G Pendl
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A Elbe
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E Serfling
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N E Harrer
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G Stingl
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T Baumruker
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Abstract

While it was recently shown that activation of dendritic cells (DC) results in the production of a number of cytokines, the signal pathways and transcription factors involved in this process have not been described. To address this issue we compared the events resulting in the activation of the human TNF-alpha promoter occurring in the fetal dendritic cell line 18 (DC18) with those in the well-characterized murine mast cell line CPII. As stimuli we employed the protein kinase C inducer, PMA, and the Ca2+ ionophore, ionomycin, both of which are known to activate a large variety of intracellular signaling pathways. In the DC18 cells, PMA alone induces the TNF-alpha promoter in a macrolide-insensitive manner. In contrast, in the mast cell line CPII, both stimuli (PMA plus ionomycin) are necessary for promoter activation which, in addition, is sensitive to immunosuppressive drugs. Mapping of the TNF-alpha promoter showed that in both cell types the so-called kappa factor binding site is the crucial promoter element for the induction. We show that in DC18 cells, this sequence is bound to and controlled by NF-kappaB proteins p50 (NF-kappaB1) and p65 (ReIA), whereas in CPII mast cells, NF-AT and AN factors are the predominant proteins that bind to and control the kappaB element of the TNF-alpha promoter. These and further experimental data indicate that in DC, NF-kappaB factors play a predominant role in the activation of the TNF-alpha promoter and, possibly, of other cytokine promoters.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 157, Issue 6
15 Sep 1996
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Induction of the TNF-alpha promoter in the murine dendritic cell line 18 and the murine mast cell line CPII is differently regulated.
E E Preischl, G G Pendl, A Elbe, E Serfling, N E Harrer, G Stingl, T Baumruker
The Journal of Immunology September 15, 1996, 157 (6) 2645-2653;

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Induction of the TNF-alpha promoter in the murine dendritic cell line 18 and the murine mast cell line CPII is differently regulated.
E E Preischl, G G Pendl, A Elbe, E Serfling, N E Harrer, G Stingl, T Baumruker
The Journal of Immunology September 15, 1996, 157 (6) 2645-2653;
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Print ISSN 0022-1767        Online ISSN 1550-6606