cAMP-induced Interleukin-10 promoter activation depends on CCAAT/enhancer-binding protein expression and monocytic differentiation.
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/EBP alpha 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.
Brenner
Susanne
S
Institute of Anatomy II, Medical School, Friedrich Schiller University, D-07740 Jena, Germany.
Prösch
Susanna
S
Schenke-Layland
Katja
K
Riese
Ulrike
U
Gausmann
Ulrike
U
Platzer
Cornelia
C
D000818:Animals; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D018387:Codon, Initiator; D000242:Cyclic AMP / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D018922:HL-60 Cells; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D009115:Muridae; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000276:immunology; D016385:TATA Box; D014158:Transcription, Genetic / Q000276:immunology*; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D018387:Codon, Initiator; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D016753:Interleukin-10; D003994:Bucladesine; D000242:Cyclic AMP