CLONING OF A HUMAN BCL-2 HOMOLOG - INFLAMMATORY CYTOKINES INDUCE HUMAN A1 IN CULTURED ENDOTHELIAL-CELLS

Bcl-2 is an intracellular membrane-associated protein that functions t o block programmed cell death. Despite recurrent exposure to cellular toxins from the circulation and tissue, endothelial cells are remarkab ly resistant to cell death. Because Bcl-2 protein levels are low or un detectable in endothelial cells, we postulated that other members of t he growing Bcl-2 family would be present in endothelial cells to provi de protection against apoptosis. Degenerate primers to two conserved r egions of the Bcl-2 family were used to amplify potential homologues i n endothelial cells. This strategy resulted in the isolation of a huma n Bcl-2 homologue related to murine A1, a recently identified member o f this family. We show here that, in endothelial cells, human A1 is ra pidly inducible by phorbol ester and the inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1 beta, but not by the growth f actors, basic fibroblast growth factor or vascular endothelial growth factor. A1 is the only known Bcl-2 family member that is inducible by inflammatory cytokines, suggesting that it may play a protective role during inflammation. Additionally, vascular smooth muscle cells and va rious nonhematopoietic tissues express human A1, indicating that human A1 is a widely expressed Bcl-2 homologue. (C) 1996 by The American So ciety of Hematology.