Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor, on the expression of adhesion molecules on human monocyte cell line.
The effect of fluvastatin, an HMG-CoA reductase inhibitor, was investigated on the adhesive interaction between U937 cells, the human monocyte cell line, and human umbilical vein endothelial cells (HUVEC), focusing on the expression of adhesion molecules. U937 treated with fluvastatin lowered the capacity for binding to HUVEC. Fluvastatin at 0.1 microM or more inhibited the expression of lymphocyte function associated antigen-1 (LFA-1) on U937 and intercellular adhesion molecule-1 (ICAM-1) on U937. The expression of ICAM-1 on HUVEC was not inhibited by fluvastatin. The inhibitory effects of fluvastatin on the expression of adhesion molecules on U937 were completely reversed by the addition of mevalonate. Because fluvastatin did not affect the expression of other cell surface markers, CD4 and CD71, the inhibitory effects of fluvastatin on adhesion molecule expression could not be attributed to the non-specific suppression of the cell. It is conceivable that cellular interaction between monocytes and endothelial cells is inhibited by fluvastatin, mediated via reducing the expression of adhesion molecules, particularly in the side of monocyte.
Niwa
S
S
Department of Pharmacology, Sandoz Tsukuba Research Institute, Ibaraki, Japan.
Totsuka
T
T
Hayashi
S
S
D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D003864:Depression, Chemical; D004797:Enzyme-Linked Immunosorbent Assay; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005434:Flow Cytometry; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008798:Mevalonic Acid / Q000494:pharmacology; D009000:Monocytes; D017035:Pravastatin / Q000494:pharmacology; D014471:Umbilical Veins
D015815:Cell Adhesion Molecules; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D000077340:Fluvastatin; D017035:Pravastatin; D008798:Mevalonic Acid