| First Author | Scheibel M | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 12 | Pages | 2621-30 |
| PubMed ID | 20975042 | Mgi Jnum | J:176877 |
| Mgi Id | MGI:5292847 | Doi | 10.1084/jem.20100864 |
| Citation | Scheibel M, et al. (2010) IkappaBbeta is an essential co-activator for LPS-induced IL-1beta transcription in vivo. J Exp Med 207(12):2621-30 |
| abstractText | Inhibitor of kappaB (IkappaB) beta (IkappaBbeta) represents one of the major primary regulators of NF-kappaB in mammals. In contrast to the defined regulatory interplay between NF-kappaB and IkappaBalpha, much less is known about the biological function of IkappaBbeta. To elucidate the physiological role of IkappaBbeta in NF-kappaB signaling in vivo, we generated IkappaBbeta-deficient mice. These animals proved to be highly refractory to LPS-induced lethality, accompanied by a strong reduction in sepsis-associated cytokine production. In response to LPS, IkappaBbeta is recruited to the IL-1beta promoter forming a complex with the NF-kappaB subunits RelA/c-Rel required for IL-1beta transcription. Further transcriptome analysis of LPS-stimulated wild-type and IkappaBbeta-deficient BM-derived macrophages revealed several other genes with known regulatory functions in innate immunity arguing that a subset of NF-kappaB target genes is under control of IkappaBbeta. Collectively, these findings provide an essential proinflammatory role for IkappaBbeta in vivo, and establish a critical function for IkappaBbeta as a transcriptional coactivator under inflammatory conditions. |
