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 alpha or interleukin-1beta, 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, NFkappaB, 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 NFkappaB activity.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Umetani M,Nakao H,Doi T,Iwasaki A,Ohtaka M,Nagoya T,Mataki C,Hamakubo T,Kodama Tdoi
10.1006/bbrc.2000.2784subject
Has Abstractpub_date
2000-06-07 00:00:00pages
370-4issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(00)92784-0journal_volume
272pub_type
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