Hypoxia enhances induction of endothelial ICAM-1: role for metabolic acidosis and proteasomes.

摘要: Intercellular adhesion molecule 1 (ICAM-1) is an important in promotion of polymorphonuclear neutrophil transendothelial migration during inflammation. Coincident with many inflammatory diseases tissue hypoxia. Thus we hypothesized that combinations hypoxia and stimuli may differentially regulate expression endothelial ICAM-1. Human cells were exposed to the presence or absence added lipopolysaccharide (LPS) examined for functional Although alone did not induce ICAM-1, combination LPS enhanced (3 +/- 0.4-fold over normoxia) ICAM-1 expression. Combinations significantly increased lymphocyte binding, such increases inhibited by addition anti-ICAM-1 antibodies antisense oligonucleotides. Hypoxic endothelia showed a > 10-fold increase sensitivity inhibitors proteasome activation, proteasome-dependent cytoplasmic-to-nuclear localization nuclear transcription factor-kappa B p65 (Rel A) subunit. Such activation correlated hypoxia-evoked decreases both extracellular intracellular pH. We conclude from these studies provides novel, stimulus induction.