Inhibition of endothelial cell adhesion molecule expression with SJC13, an azaindolidine derivative, in vitro.
Stimulation of cultured human umbilical vein endothelial cells (HUVEC) with lipopolysaccharide (LPS) induces adherences for human promyelocytic cell line HL60. Adherence of HL60 cells to HUVEC stimulated with LPS for 4h was completely inhibited by pretreatment with SJC13, an azaindolidine derivative. The mechanism whereby SJC13 inhibits the adhesiveness of HUVEC was investigated. Pretreatment of SJC13 inhibited LPS-induced expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1), in HUVEC, determined by flow cytometry and cellular enzyme-linked immunosorbent assay (cell-ELISA). The inhibitory activity was concentration dependent between 62.5 and 1,000 micrograms/ml. SJC13 also selectively inhibited LPS-induced increases in E-selectin and VCAM-1 mRNAs, indicating that the action of SJC13 is to inhibit synthesis of these molecules. These data demonstrate that SJC13 is capable of selectively inhibiting the expression of E-selectin and VCAM-1, but not ICAM-1, in endothelial cells.
Sakai
A
A
Research Laboratory, Zenyaku Kogyo Co. Ltd., Tokyo, Japan.
D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007093:Imidazoles; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C102823:SJC 13