IκBη, a nuclear IκB protein, positively regulates the NF-κB-mediated expression of proinflammatory cytokines

NF-kappa B is a key mediator for inducible transcription of various proinflammatory genes in innate immune responses, and its activity is strictly regulated by several I kappa B proteins. Although signaling pathways leading from pattern recognition receptors to NF-kappa B's activation in the cytoplasm have been studied extensively, the detail regulatory mechanisms of NF-kappa B-mediated transcriptional activity in the nucleus still remain unclear. Here we describe a unique member of the nuclear I kappa B protein family, I kappa B eta. In a gene expression analysis of dendritic cells, we found a unique gene encoding an uncharacterized protein with ankyrin repeats. As it was structurally related to the I kappa B family, the protein was named "I kappa B eta" and further characterized in the innate immune response. I kappa B eta was widely expressed in various tissues and predominantly located in the nucleus. Moreover, biochemical analysis showed that I kappa B eta associated with the p50 subunit of NF-kappa B. Knockdown of I kappa B eta by siRNA suppressed the transcription of a subset of NF-kappa B-mediated proinflammatory cytokines in LPS-stimulated and poly (I:C)-transfected macrophages. These results indicate that I kappa B eta regulates the NF-kappa B-mediated transcription of a wide variety of proinflammatory genes, playing a crucial role in the regulation of innate immune responses.