Overexpression of A1, an NF-kappa B-inducible anti-apoptotic Bcl gene, inhibits endothelial cell activation

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 prot ecting EC from apoptosis, A1 inhibits EC activation and its associated expr ession of proinflammatory proteins by inhibiting the transcription factor n uclear factor (NF)-kappa B, This new anti-inflammatory function gives a bro ader dimension to the protective role of A1 in EC, We also show that activa tion of NF-kappa B is essential for the expression of A1. Taken together, o ur data suggest that A1 downregulates not only the pro-apoptotic and pro-in flammatory response, but also its own expression, thus restoring a quiescen t phenotype to EC. (C) 1999 by The American Society of Hematology.