title: Overexpression of A1, an NF-kappaB-inducible anti-apoptotic bcl gene, inhibits endothelial cell activation.
abstract: A1 is an anti-apoptotic bcl gene that is expressed in endothelial cells (EC) in response to pro-inflammatory stimuli. We show that in addition to protecting EC from apoptosis, A1 inhibits EC activation and its associated expression of pro-inflammatory proteins by inhibiting the transcription factor nuclear factor (NF)-kappaB. This new anti-inflammatory function gives a broader dimension to the protective role of A1 in EC. We also show that activation of NF-kappaB is essential for the expression of A1. Taken together, our data suggest that A1 downregulates not only the pro-apoptotic and pro-inflammatory response, but also its own expression, thus restoring a quiescent phenotype to EC.
authors.affiliation: Immunobiology Research Center, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Stroka
authors.forename: A Z
authors.initials: AZ
authors.lastname: Badrichani
authors.forename: F H
authors.initials: FH
authors.lastname: Bach
authors.forename: C
authors.initials: C
authors.lastname: Ferran
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins; D006801:Humans; D007249:Inflammation; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins
chemical_list: C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051818:Replication Protein C