摘要
目的研究氟伐他汀抑制干扰素-γ(IFN-γ)诱导的内皮细胞表面主要组织相容性抗原复合物Ⅱ(MHCⅡ)表达的作用,并研究其抑制作用的机理。方法通过流式细胞仪检测分析MHCⅡ在内皮细胞中的表达,通过RT-PCR检测Ⅱ类反式激活因子(CⅡTA)mRNA的生成,通过Western blot分析信号转导和转录激活因子1(STAT1)的总量和磷酸化STAT1(P-STAT1)。结果氟伐他汀预处理可以抑制由IFN-γ刺激诱导的内皮细胞表面MHCⅡ表达,RT-PCR分析表明CⅡTA mRNA的诱导生成可以被氟伐他汀阻断。Western blot分析表明氟伐他汀预处理并不影响STAT1的总量和在IFN-γ刺激后STAT1的磷酸化。结论在内皮细胞中,氟伐他汀预处理可以抑制由IFN-γ刺激诱导的CⅡTA mR- NA的表达,并因此抑制了细胞表面MHCⅡ表达,这种抑制作用主要发生在CⅡTA的转录水平,可能与转录因子和CⅡTA启动子的结合有关。
Objective To study the effect of fluvastatin on inteferon（IFN）-γ-induced major histocompafibihty complex class Ⅱ （MHC Ⅱ ） expression in endothelial cells, and to study the mechanism of the inhibitory effect. Methods MHC Ⅱ expression in endothelial cells was detected by flow cytometry. Induction of class Ⅱ transactivator （CⅡ TA） mRNA was detected by reverse transeription-polymerase chain reaction （RT-PCR） analysis. Signal transducer and activator of transcription 1 （STAT1） and STAT1 phosphorylation were detected by Westem blot. Results Fluvastatin pretreatment inhibited MHC Ⅱ expression in endothelial ceils induced by IFN-γ. RT-PCR analysis demonstrated that the induction of C Ⅱ TA mRNA was abrogated by fluvastatin. Western blot demonstrated that IFN-γ induced STAT1 phosphorylation was not affected by fluvastatin. Condusion Fluvastatin pretreatment inhibits C Ⅱ TA and consequent MHC Ⅱ expression inducted by IFN-7 in endothelial ceil. 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.
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2006年第6期489-493,共5页
Chinese Journal of Microbiology and Immunology
基金
国家重点基础研究发展计划(973计划
No.2003CB515500)
关键词
氟伐他汀
内皮细胞
MHCⅡ
CⅡTA
STAT1
Fluvastafin
Endothelial ceil
Histocompatibility complex class Ⅱ
Class Ⅱ transactivator
Signal transducer and activator of transcription 1
