C/EBP beta enhances IL-4 but impairs IL-2 and IFN-gamma induction in T cells

C/EBP transcription factors have been described to control the activity of the human IL-4 promoter. The C/EBP binding sites within the IL-4 promoter o verlap with composite NF-AT and AP-1 binding motifs. We show here that simi lar binding sites are part of the murine IL-4 promoter. Retroviral overexpr ession of C/EBP beta in murine EL-4 thymoma cells led to a strong induction of endogenous IL-4 and a reduction in IL-2 and IFN-gamma expression. Simil arily, in primary murine T cells C/EBP beta induction resulted in an increa se in IL-4 levels, whereas in human Jurkat T cells a decrease in IL-2 RNA w as detected. Like AP-1, C/EBP factors belong to the large class of basic le ucine zipper proteins. However, unlike AP-1, C/EBP beta does not act in syn ergy with NF-AT in the induction of the murine IL-4 promoter. instead, both factors compete in their binding to the P4/Pu-b(D) site, one of the most i mportant sequence elements of the IL-4 promoter. Whereas NF-AT factors requ ire high levels of free Ca2+ and calcineurin activity for induction, C/EBP induction in T cells is Ca2+/calcineurin independent. These observations su ggest that various induction conditions lead to the activation of transcrip tion factors, inducing IL-4 promoter activity at specific developmental sta ges of T cells.