The proteasome pathway is required for cytokine-induced endothelial-leukocyte adhesion molecule expression

Immunity. 1995 May;2(5):493-506. doi: 10.1016/1074-7613(95)90030-6.

Abstract

Multiple cell adhesion proteins are up-regulated in vascular endothelial cells in response to TNF alpha and other inflammatory cytokines. This increase in cell adhesion gene expression is thought to require the transcription factor NF-kappa B. Here, we show that peptide aldehyde inhibitors of the proteasome, a multicatalytic protease recently shown to be required for the activation of NF-kappa B, block TNF alpha induction of the leukocyte adhesion molecules E-selectin, VCAM-1, and ICAM-1. Striking functional consequences of this inhibition were observed in analyses of leukocyte-endothelial interactions under defined flow conditions. Lymphocyte attachment to TNF alpha-treated endothelial monolayers was totally blocked, while neutrophil attachment was partially reduced but transmigration was essentially prevented.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Calpain / antagonists & inhibitors
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Cysteine Endopeptidases / metabolism*
  • E-Selectin
  • Endothelium, Vascular / metabolism
  • Gene Expression / drug effects
  • Humans
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-8 / genetics
  • Leukocytes / cytology
  • Leupeptins / pharmacology
  • Molecular Sequence Data
  • Multienzyme Complexes / metabolism*
  • NF-kappa B / metabolism*
  • Oligodeoxyribonucleotides / metabolism
  • Proteasome Endopeptidase Complex
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / genetics
  • Time Factors
  • Transcription Factor RelB
  • Transcription Factors*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1

Substances

  • Cell Adhesion Molecules
  • E-Selectin
  • Interleukin-8
  • Leupeptins
  • Multienzyme Complexes
  • NF-kappa B
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins
  • RELB protein, human
  • RNA, Messenger
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • carbobenzoxy-leucyl-leucyl-norvalinal
  • acetylleucyl-leucyl-norleucinal
  • Intercellular Adhesion Molecule-1
  • Transcription Factor RelB
  • Calpain
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde