In vivo binding of NF-κB to the IκBβ promoter is insufficient for transcriptional activation

Despite certain structural and biochemical similarities, differences exist in the function of the NF-kappa B (nuclear factor kappa B) inhibitory proteins I kappa B alpha (inhibitory kappa B alpha) and I kappa B beta. The functional disparity arises in part from variance at the level of gene regulation. and in particular from the substantial induction of I kappa B alpha, but not I kappa B beta, gene expression post-NF-kappa B activation. In the present study. we probe the differential effects of IL (interleukin)1,8 on induction of I kappa B alpha and perform the first characterization of the human I kappa B beta promoter. A consensus NF-kappa B-binding site, capable of binding NF-kappa B both in vitro and in vivo, is found in the I kappa B beta gene 5' flanking region. However, the I kappa B beta promoter was not substantially activated by pro-inflammatory cytokines, such as IL-1,6 and tumour necrosis factor a, that are known to cause strong activation of NF-kappa B. Furthermore, in contrast with I kappa B alpha, NF-kappa B activation did not increase expression of endogenous I kappa B beta as assessed by analysis of mRNA and protein levels.