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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.
Thomas et al. (Fri,) studied this question.