Enhancement of MMP-9 activity in THP-1 cells by 7-ketocholesterol and its suppression by the HMG-CoA reductase inhibitor fluvastatin.
We investigated the effect of 7-ketocholesterol (7-KCHO) on the activity of matrix metalloproteinase (MMP-9) in human monocytic THP-1 cells, and the inhibition of this effect by fluvastatin. In cells incubated with 7-KCHO or cholesterol, the activity of MMP-9 was enhanced, accompanying an increase in the secretion of MMP-9 proenzyme (pro-MMP-9). However, the activity of MMP-9 and the amount of pro-MMP-9 were significantly greater following incubation with 7-KCHO than cholesterol. Neither 7-KCHO nor cholesterol influenced the amount of tissue inhibitor of metalloproteinase (TIMP)-1 secreted by THP-1 cells. When fluvastatin was added to the cells, the MMP-9 activity stimulated by 7-KCHO or cholesterol decreased significantly, accompanying a decrease in the secretion of pro-MMP-9 and TIMP-1. The inhibition of pro-MMP-9 secretion by fluvastatin was stronger in the cells incubated with 7-KCHO than with cholesterol. These results suggest that 7-KCHO activates macrophage and enhances MMP-9 activity, and its effects may be inhibited by fluvastatin.
Ozaki
Hiroshi
H
Department of Internal Medicine, Sakura Hospital, Toho University School of Medicine, Chiba, Japan.
Miyashita
Yoh
Y
Watanabe
Hitoshi
H
Shirai
Kohji
K
D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007653:Ketocholesterols / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D007653:Ketocholesterols; D019715:Tissue Inhibitor of Metalloproteinase-1; D000077340:Fluvastatin; D020780:Matrix Metalloproteinase 9; C003001:7-ketocholesterol