n-(n-(3-5-difluorophenacetyl)alanyl)phenylglycine-tert-butyl-ester and Appendicitis

Endothelial upregulation of adhesion molecules serves to recruit leukocytes to inflammatory sites and appears to be promoted by NOTCH1; however, current models based on interactions between active NOTCH1 and NF-κB components cannot explain the transcriptional selectivity exerted by NOTCH1 in this context.. Observing that Cre/Lox-induced conditional mutations of endothelial Notch modulated inflammation in murine contact hypersensitivity, we found that IL (interleukin)-1β stimulation induced rapid recruitment of RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) to genomic sites occupied by NOTCH1-RBPJ (recombination signal-binding protein for immunoglobulin kappa J region) and that NOTCH1 knockdown reduced histone H3K27 acetylation at a subset of NF-κB-directed inflammatory enhancers.. Our findings reveal that NOTCH1 signaling supports the expression of a subset of inflammatory genes at the enhancer level and demonstrate how key signaling pathways converge on chromatin to coordinate the transition to an infla mmatory endothelial phenotype.

Topics: Acetylation; Animals; Appendicitis; Cells, Cultured; Dermatitis, Contact; Dipeptides; Disease Models, Animal; Endothelial Cells; Female; Gene Expression Regulation; Histones; Human Umbilical Vein Endothelial Cells; Humans; Immunoglobulin J Recombination Signal Sequence-Binding Protein; Inflammation; Interleukin-1beta; Male; Mice, Inbred C57BL; Mice, Transgenic; Phenotype; Receptor, Notch1; Signal Transduction; Transcription Factor RelA