Effect of selective proteasome inhibitors on TNF-induced activation of primary and transformed endothelial cells

Theodore J. Kalogeris, F. Stephen Laroux, Adam Cockrell, Hiroshi Ichikawa, Naotsuka Okayama, Travis J. Phifer, J. Steven Alexander, Matthew B. Grisham
1999 American Journal of Physiology - Cell Physiology  
Effect of selective proteasome inhibitors on TNF-induced activation of primary and transformed endothelial cells. Am. J. Physiol. 276 (Cell Physiol. 45): C856-C864, 1999.-The objective of this study was to assess the effects of two structurally distinct yet selective proteasome inhibitors (PS-341 and lactacystin) on leukocyte adhesion, endothelial cell adhesion molecule (ECAM) expression, and nuclear factor-B (NF-B) activation in tumor necrosis factor (TNF)-␣-stimulated human umbilical vein
more » ... thelial cells (HUVEC) and the transformed, HUVEC-derived, ECV cell line. We found that TNF (10 ng/ml) significantly 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 well as intercellular adhesion molecule 1 (ICAM-1; in HUVEC and ECV). Pretreatment of HUVEC with lactacystin completely blocked TNF-stimulated PMN adhesion, partially blocked U-937 adhesion, and completely blocked TNF-stimulated ECAM expression. Lactacystin attenuated TNF-stimulated ICAM-1 expression in ECV. Pretreatment of HUVEC with PS-341 partially blocked TNFstimulated leukocyte adhesion and ECAM expression. These effects of lactacystin and PS-341 were associated with inhibitory effects on TNF-stimulated NF-B activation in both HUVEC and ECV. Our results demonstrate the importance of the 26S proteasome in TNF-induced activation of NF-B, ECAM expression, and leukocyte-endothelial adhesive interactions in vitro. inflammatory mediators; nuclear factor-B; adhesion molecules; leukocyte adhesion; U-937 cell line; neutrophils; human umbilical vein endothelial cells; ECV cell line The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
doi:10.1152/ajpcell.1999.276.4.c856 fatcat:alpx65f5ozelpkfu3rseoyuo54