期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：26
页码：11924-11929
DOI：10.1073/pnas.0913179107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
