摘要
目的:研究FK228对TNF-α诱导的人肝癌细胞HepG2核转录因子κB(nuclear factor-κB,NF-κB)活化及炎症因子IL-6、IL-8转录的影响。方法:培养的HepG2细胞分为对照组、TNF-α刺激组和FK228干预组。分别用TNF-α刺激和FK228+TNF-α共同作用,免疫印迹(Western blot)法分析细胞核中NF-κBp65及其细胞浆中抑制因子IκBα的表达;RT-PCR对炎症因子IL-6、IL-8 mRNA作半定量分析。结果:FK228(4～32μg·L^(-1))干预组与TNF-α刺激组比较,细胞核内NF-κB显著减少(P<0.01);FK228(8～32μg·L^(-1))减少胞浆中IκBα的降解且各组之间差异有统计学意义(P<0.01);FK228降低TNF-α诱导的IL-6、IL-8 mRNA表达,FK228干预组与TNF-α刺激组相比,差异具统计学意义(P<0.01)。结论:FK228减少胞浆中IκBα降解、阻碍NF-κB的过度活化可能是降低炎症因子释放、发挥抗炎作用的重要机制。
AIM： To investigate the effect of FK228 on the TNF-α-induced activation of NF-κBp65 and transcription of proinflammatory cytokines gene such as IL-6 and IL-8 in human hepatoma cell line HepG2. METHODS： Cultured HepG2 were divided into 3 groups, normal control group, TNF-α stimulation group, and interference group （FK228＋TNF-α）. The expression of NF-κBp65 in the nucleus and IκBα in the cytoplasm were measured by Western blot. RT-PCR was performed for semi-quantitative analysis of the changes on IL-6 and IL-8 mRNA levels. RESULTS： Various concentrations of histone deacetylase inhibitor （HDIs） such as FK228 （4-32 μg·L^-1） inhibited TNF-α-induced nuclear translocation of NF-κB. The interference groups （FK228＋TNF-α） were significantly different from TNF-α stimulation group （P 〈 0.01 ）. FK228 （8-32 μg·L^-1） decreased the degradation of IκBα and each group was different from others （P 〈 0.01 ）. FK228 down-rugulate TNF-α-induced mRNA level of IL-6 and IL-8 expressions. The interference groups （FK228＋TNFα） were significantly different from TNF-α stimulation group （P 〈 0.01 ）. CONCLUSION： The inhibition of FK228 on activation of NF-κB by reducing degradation of IκBα and the mechanisim of proinflammatory cytokines reduction may implicate for anti-inflammatory effects.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2007年第11期813-817,共5页
Chinese Journal of New Drugs and Clinical Remedies
