| First Author | Brenner S | Year | 2003 |
| Journal | J Biol Chem | Volume | 278 |
| Issue | 8 | Pages | 5597-604 |
| PubMed ID | 12493739 | Mgi Jnum | J:81998 |
| Mgi Id | MGI:2450495 | Doi | 10.1074/jbc.M207448200 |
| Citation | Brenner S, et al. (2003) cAMP-induced Interleukin-10 promoter activation depends on CCAAT/enhancer-binding protein expression and monocytic differentiation. J Biol Chem 278(8):5597-604 |
| abstractText | 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. |
