Tj. Kalogeris et al., Effect of selective proteasome inhibitors on TNF-induced activation of primary and transformed endothelial cells, AM J P-CELL, 45(4), 1999, pp. C856-C864
The objective of this study was to assess the effects of two structurally d
istinct yet; selective proteasome inhibitors (PS-341 and lactacystin) on le
ukocyte adhesion, endothelial cell adhesion molecule (ECAM) expression, and
nuclear factor-kappa B (NF-kappa B) activation in tumor necrosis factor (T
NF)-alpha-stimulated human umbilical vein endothelial cells (HUVEC) and the
transformed, HUVEC-derived, ECV cell line. We found that TNF (10 ng/ml) si
gnificantly enhanced U-937 and polymorphonuclear neutrophil (PMN) adhesion
to HUVEC but not to ECV; TNF also significantly enhanced surface expression
of vascular cell adhesion molecule 1 and E-selectin (in HUVEC only), as we
ll as intercellular adhesion molecule 1 (ICAM-1; in HUVEC and ECV). Pretrea
tment of HUVEC with lactacystin completely blocked TNF-stimulated PMN adhes
ion, partially blocked U-937 adhesion, and completely blocked TNF-stimulate
d ECAM expression. Lactacystin attenuated TNF-stimulated ICAM-1 expression
in ECV. Pretreatment of HUVEC with PS-341 partially blocked. TNF-stimulated
leukocyte adhesion and ECAM expression. These effects of lactacystin and P
S-341 were associated with inhibitory effects on TNF-stimulated NF-kappa B
activation in both HUVEC and ECV. Our results demonstrate the importance of
the 26S proteasome in TNF-induced activation of NF-kappa B, ECAM expressio
n, and leukocyte-endothelial adhesive interactions in vitro.