Inhibition of major histocompatibility complex classIIexpression in endothelial cells by fluvastatin
Objective To study the effect of fluvastatin on interferon(IFN)-γ-induced major histocom-patibility complex classⅡ(MHCⅡ) expression in endothelial cells, and to study the mechanism of the inhibitory effect. Methods MHCⅡexpression in endothelial cells was detected by flow cytometry. Induction of classⅡtransactivator (CⅡTA) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Signal transducer and activator of transcription 1 (STAT1) and STAT1 phosphorylation were detected by Western blot. Results Fluvastatin pretreatment inhibited MHCⅡexpression in endothelial cells induced by IFN-γ. RT-PCR analysis demonstrated that the induction of CⅡTA mRNA was abrogated by fluvastatin. Western blot demonstrated that IFN-γinduced STAT1 phosphorylation was not affected by fluvastatin. Conclusion Fluvastatin pretreatment inhibits CⅡTA and consequent MHCⅡexpression inducted by IFN-γin endothelial cell. This inhibitory effect may occurs at the level of transcription and is directed, at least in part, at the CⅡTA promoter. These results explain some of the beneficial effects of HMG-CoA reductase inhibitors in transplantation.