CYTOKINE-INDUCED EXPRESSION OF PORCINE INHIBITOR OF APOPTOSIS PROTEIN(IAP) FAMILY MEMBER IS REGULATED BY NF-KAPPA-B

The inhibitor of apoptosis (lap) proteins belong to a gene family that protect certain cell to undergo programmed cell death in response to a variety of stimuli. By differential screening we have identified a c DNA clone, designated piap, in porcine aortic endothelial cells (PAEC) that turned out by sequence comparison to be a porcine member of the lap family. The expression of piap is strongly up-regulated upon treat ment of endothelial cells (EC) with inflammatory cytokines TNF-alpha, IL-1 beta, and LPS. In EC these stimuli lead to the activation of nucl ear transcription factor kappa B (NF-kappa B) that plays a role in cou ntering TNF-alpha induced apoptosis. We demonstrate that adenovirus me diated overexpression of I kappa B alpha, an inhibitor of NF-kappa B s uppresses the expression of piap in response to TNF-alpha suggesting t hat piap is one of the NF-kappa B regulated genes that operates to pre vent programmed cell death of EC in inflammation. (C) 1998 Academic Pr ess.