A novel cell adhesion inhibitor, K-7174, reduces the endothelial VCAM-1 induction by inflammatory cytokines, acting through the regulation of GATA

Michihisa Umetani, Hiroshi Nakao, Takeshi Doi, Akio Iwasaki, Manami Ohtaka, Takao Nagoya, Chikage Mataki, Takao Hamakubo, Tatsuhiko Kodama

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

A novel inhibitor for the adhesion of monocytes to cytokine-stimulated endothelial cells, K-7174, was selected by an assay system using the cultured human monocytic cells and human endothelial cells. K-7174 inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) induced by either tumor necrosis factor α or interleukin-1β, without affecting the induction of intercellular adhesion molecule-1 or E-selectin. K-7174 had no effect on the stability of VCAM-1 mRNA. Electrophoretic mobility shift assay revealed that its inhibitory effect on VCAM-1 induction was mediated by an effect on the binding to the GATA motifs in the VCAM-1 gene promoter region. K-7174 did not influence the binding to any of the following binding motifs: octamer binding protein, AP-1, SP-1, ets, NFκB, or interferon regulatory factor. These results suggest that the regulation of GATA binding may become a new target for anti-inflammatory drug development, acting through a mechanism independent from NFκB activity. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)370-374
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume272
Issue number2
DOIs
StatePublished - Jun 7 2000

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Keywords

  • Cell adhesion molecule
  • GATA
  • HUVEC
  • NFκB
  • TNFα
  • VCAM-1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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