“…Finally, we chose to examine the role of two other transcription factor families, CREB and C/EBP, in basal and calcineurin-activated IL-6 promoter activity for three reasons: 1) binding sites for these transcription factors have been previously identified in the IL-6 promoter region, and they are known to regulate IL-6 promoter activity in other cell types (13,18,37,54); 2) their activity can be altered by calcineurin signaling (7,28,31,56,64); 3) repression of MEF-2 activity by MITR cotransfection was unable to eliminate all of the calcineurin induction of the IL-6 promoter, suggesting that other pathways contribute to this response. We found that, as has been shown previously for other cell types (13,18,37,54), mutation of the CREB or C/EBP binding sites alone significantly attenuated basal IL-6 promoter activity, and mutation of both together decreased basal IL-6 promoter activity to ϳ10% of wild type.…”