Roles of CCAAT/enhancer-binding protein in transcriptional regulation of the human IL-5 gene.

Interleukin-5 (IL-5) plays a critical role in the pathogenesis of eosinophil-associated allergic disorders, such as asthma. IL-5 may also play a major role in the development of eosinophilia-associated lymphoproliferative disorders caused by human T lymphotropic virus type I (HTLV-I). In this study, we have investigated the control mechanisms for IL-5 production and found that ectopic expression of NF-IL6 (C/EBPbeta) increases endogenous IL-5 mRNA expression. The IL-5 promoter contains four C/EBP consensus sequences. We show here that one of the C/EBP site at - 235 promoter region binds to NF-IL6 protein with high affinity and interacts with NF-IL6 and NF-IL6beta (C/EBPdelta) in Jurkat T cells. Mutations within the C/EBP sequence reduced the promoter activity in response to T cell activation by more than 50 %. In addition, we show that in vivo inducible expression of Tax protein in Jurkat T cells stably transfected with Tax further increased ionomycin plus phorbol ester stimulated IL-5 promoter activity. The effect of Tax on IL-5 promoter activity was abolished when the C/EBP site was mutated. Thus, the C/EBP site may be also involved in HTLV-I Tax-mediated up-regulation of IL-5 gene expression. Our data suggest that C/EBP proteins may regulate IL-5 gene expression in response to different stimulation signals.