Diclofenac inhibits endothelial cell adhesion molecule expression induced with lipopolysaccharide.
Stimulation of cultured human umbilical vein endothelial cells (HUVEC) with lipopolysaccharide (LPS) induces adherence for human promyelocytic cell line HL60. Adherence of HL60 cells to HUVEC stimulated with LPS for 4 hr and for 24 hr were completely inhibited by pretreatment with diclofenac. While some other nonsteroidal antiinflammatory drugs (NSAIDs), such as ketoprofen, phenylbutazone, indomethacin, ibuprofen and acetylsaticylic acid, did not inhibit. The mechanism whereby diclofenac inhibits the adhesiveness of HUVEC was investigated. Pretreatment of diclofenac inhibited LPS-induced expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in HUVEC, determined by flow cytometry and a cellular enzyme-linked immunosorbent assay (cell-ELISA). The inhibitory activity was concentration dependent between 15.6 and 250 micrograms/ml. Diclofenac also inhibited LPS-induced increases in E-selectin, ICAM-1 and VCAM-1 mRNAs, indicating that the action of diclofenac is to inhibit synthesis of these molecules. These data demonstrate that diclofenac is capable of inhibiting the expression of E-selectin, ICAM-1 and VCAM-1 in HUVEC.
Sakai
A
A
Research Laboratory, Zenyaku Kogyo Co., Ltd., Tokyo, Japan.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002478:Cells, Cultured; D004008:Diclofenac / Q000494:pharmacology*; D019040:E-Selectin / Q000032:analysis / Q000235:genetics; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004008:Diclofenac