Interleukin-1beta (IL-1beta) is a potent inhibitor of platelet-derived growth factor ot receptor (PDGFRalpha) expression in MG-63 cells. Its effect is mediated at the transcriptional level, but the transcription factors involved in this process are unknown. In the current study, we found that IL-1beta could inhibit the PDGFRalpha gene promoter activity, and this effect was strongly correlated with increased binding of CCAAT/enhancer-binding protein (C/EBP) to the responsive prornoter region. In addition, forced expression of C/EBPbeta could mimic the IL-1beta effect on the promoter activity, but subsequent mutation analysis of the C/EBP binding sites indicated that direct C/EBP binding to the promoter is not required for the IL-1beta response. However, our data clearly demonstrated that the C/EBP binding site at position-162 relative to the transcriptional start site is essential for high basal level PDGFRalpha promoter activity. (C) 2004 Elsevier Inc. All rights reserved.