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Originally published In Press as doi:10.1074/jbc.M207448200 on December 18, 2002

J. Biol. Chem., Vol. 278, Issue 8, 5597-5604, February 21, 2003
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cAMP-induced Interleukin-10 Promoter Activation Depends on CCAAT/Enhancer-binding Protein Expression and Monocytic Differentiation*

Susanne BrennerDagger , Susanna PröschDagger §, Katja Schenke-Layland, Ulrike Riese, Ulrike Gausmann, and Cornelia Platzer||

From the Institute of Anatomy II, Medical School, Friedrich Schiller University, D-07740 Jena, Germany, the § Department of Virology, Medical School Charité, Humboldt University, D-10098 Berlin, Germany, and the  Department of Genome Analysis, Institute of Molecular Biotechnology, D-07749 Jena, Germany

The molecular mechanisms underlying the regulation of interleukin (IL)-10 transcription in monocytic cells by various stimuli during inflammation and the stress reaction are not fully understood. Recently, we provided evidence that stress-induced IL-10 promoter activation in monocytic cells is mediated by catecholamines via a cAMP-dependent signaling pathway including CREB/ATF (cAMP-responsive element binding protein/activating transcription factor) binding to two CRE motifs. However, the mutation of these sites diminished cAMP responsiveness by only 50%, suggesting a role for additional transcription factors and elements in the cAMP-dependent regulation of the human IL-10 promoter. Here, we analyze the functional role of one such factor, C/EBP, in two cell lines of myelomonocytic origin, THP-1 and HL-60, which are known to differ in their differentiation status and C/EBP protein content. We show that the level of basal as well as cAMP-stimulated IL-10 transcription depends on the expression of C/EBPalpha and beta  and their binding to three motifs in the promoter/enhancer region. The C/EBP5 motif, which is located between the TATA-box and the translation start point, is essential for the C/EBP-mediated constitutive and most of the cAMP-stimulated expression as its mutation nearly abolished IL-10 promoter activity. Our results suggest a dominant role of C/EBP transcription factors relative to CREB/ATF in tissue-specific and differentiation-dependent IL-10 transcription.

* This work was supported by Deutsche Forschungsgemeinschaft Pl 163/4-3.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Both authors contributed equally to this work.

|| To whom correspondence should be addressed. Tel.: 49-3641-938570; Fax: 49-3641-938552; E-mail: cplatzer@mti-n.uni-jena.de.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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