Critical role of C/EBPdelta and C/EBPbeta factors in the stimulation of the cyclooxygenase-2 gene transcription by interleukin-1beta in articular chondrocytes.

Thomas B, Berenbaum F, Humbert L, Bian H, Béréziat G, Crofford L, Olivier JL
Eur J Biochem. 2000 267 (23): 6798-809

PMID: 11082190 · DOI:10.1046/j.1432-1033.2000.01778.x

The activity of the [-831; +103] promoter of the human cyclooxygenase-2 gene in cultured rabbit chondrocytes is stimulated 2.9 +/- 0.3-fold by interleukin-1beta and this stimulation depends on [-132; -124] C/EBP binding-and [-223; -214] NF-kappaB binding-sites. The C/EBPbeta and C/EBPdelta factors bind to the [-132; -124] sequence. The [-61; -53] sequence is also recognized by C/EBPbeta and C/EBPdelta as well as USF. Mutation of the whole [-61; -53] sequence abolished the stimulation of transcription but single mutations of the C/EBP or USF site did not alter the activity of the promoter, suggesting that the factors bound to the proximal [-61; -53] sequence interact with different members of the general transcription machinery. The [-223; -214] site binds only the p50/p50 homodimer and a non-rel-related protein, but not the transcriptionally active heterodimer p50/p65. The p50/p50 homodimer could interact with the C/EBP family members bound to the [-132; -124] sequence for full stimulation of the COX-2 transcription by interleukin-1beta in chondrocytes. By contrast, the [-448; -449] sequence binds with a low affinity both the p50/p50 homodimeric and p50/p65 heterodimeric forms of NF-kappaB but has no role in the regulation of the human COX-2 promoter in chondrocytes.

MeSH Terms (32)

Animals Base Sequence Binding Sites Cartilage, Articular CCAAT-Enhancer-Binding Protein-beta CCAAT-Enhancer-Binding Protein-delta CCAAT-Enhancer-Binding Proteins Cell Nucleus Cells, Cultured Chloramphenicol O-Acetyltransferase Chondrocytes Cyclooxygenase 2 Female Gene Deletion Gene Expression Regulation Humans Interleukin-1 Isoenzymes Kinetics Membrane Proteins Models, Biological Molecular Sequence Data Mutagenesis Plasmids Promoter Regions, Genetic Prostaglandin-Endoperoxide Synthases Protein Binding Proto-Oncogene Proteins c-rel Rabbits Sequence Homology, Nucleic Acid Transcription, Genetic Transcription Factors

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