¸ñÀû: We recently showed that chronic cholesterol depletion in NCI-H292
cells by lovastatin suppressed IL-1¥â-induced MUC5AC gene
expression. Because lots of cholesterol-lowering drugs exist, we
sought to investigate which statin drug is most effective and
safe to reduce MUC5AC gene expression. We also considered whether
this action of statin is related to IL-1 receptor and mitogen-
activated protein kinase (MAPK) activity. ¹æ¹ý:Five statins such as atorvastatin, cerivastatin, fluvastatin,
lovastatin, and simvastatin were tested. NCI-H292 cells were
pretreated with 10 ¥ìM of each statin for 1 hour, 10 ng/mL of IL-
1¥â was added and cotreated with statin for 24 hours. MUC5AC mRNA
expression was then determined by RT-PCR and real-time PCR. Cell
survival was determined with cell proliferation assay.
Cholesterol depletion by lovastatin was measured by modified
microenzymatic fluorescence assay and filipin staining. The
phosphorylation of IL-1 receptor, ERK, and p38 MAPK was analyzed
by Western blot. °á°ú:IL-1¥â-induced MUC5AC mRNA expression was significantly decreased by 10 ¥ìM atorvastatin, cerivastatin, and lovastatin as 1.4 + 0.2, 3.2 + 0.5, and 1.8 + 0.2 fold increase, respectively, compared to the control group. Among them, atorvastatin was the most potent to reduce MUC5AC mRNA expression and this reduction was dose-dependent. However, MUC5AC expression was not decreased by fluvastatin and simvastatin. In 10 ¥ìM concentration, cell survival was maintained above 80% in all statins. Cholesterol in the plasma membrane was significantly depleted by all statins. In this result, atorvastatin was selected as the most potent and safe statin to suppress MUC5AC gene expression. This decrease of MUC5AC expression by atorvastatin occurred IL-1 receptor specifically. Atorvastatin suppressed the activation of p38 MAPK but not ERK1/2. °á·Ð:This result suggests that atorvastatin may be considered an
antihypersecretory method. |