interleukin-8 and carbobenzoxy-leucyl-leucyl-norvalinal

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.

Topics: Base Sequence; Calpain; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; Cysteine Endopeptidases; E-Selectin; Endothelium, Vascular; Gene Expression; Humans; In Vitro Techniques; Intercellular Adhesion Molecule-1; Interleukin-8; Leukocytes; Leupeptins; Molecular Sequence Data; Multienzyme Complexes; NF-kappa B; Oligodeoxyribonucleotides; Proteasome Endopeptidase Complex; Proto-Oncogene Proteins; RNA, Messenger; Time Factors; Transcription Factor RelB; Transcription Factors; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1