组蛋白去乙酰化酶1通过NF-κB调控炎症性滑膜细胞表达Cyr61

HDAC1 regulates expression of Cyr61 in inflammatory synovial cells through NF-κB

本研究探讨组蛋白去乙酰化酶(histone deacetylase enzyme,HDAC)在IL-17上调类风湿性关节炎(rheumatoid arthritis,RA)滑膜细胞Cyr61表达过程中的调控机制。通过real-time PCR分别检测了滑膜组织和细胞中的HDAC表达格局,HDAC抑制剂曲古抑菌素(trichostatin,TSA)和尼克酰胺(nicotinamide,NAM)作用于滑膜细胞及其相关信号通路变化后IL-17上调Cyr61的表达格局。结果显示:RA病人滑膜组织和细胞中高表达HDAC1,并且IL-17刺激又能促进滑膜细胞的HDAC1表达升高。TSA能上调IL-17诱导滑膜细胞Cyr61的表达,而NAM不能。加入NF-κB特异性抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)能够明显的抑制TSA对Cyr61的上调作用。以上结果提示HADC1通过作用于转录因子NF-κB参与了IL-17上调滑膜细胞表达Cyr61的过程。

We investigated the role of histone deacetylase enzyme 1 （HDAC1） in IL-17-induced upregulation of Cyr61 in synovial cells of rheumatoid arthritis （RA）. The pattern of expression of HDAC1 in synovial tissues and synoviocytes was examined by real-time PCR, and so do the expression pattern of Cyr61 induced by IL-17 after adding HDAC inhibitor trichostatin（TSA）/ niacinamide（NAM） and/or specific inhibitor of NF-κB（PDTC） to RA synovial cells. The results showed that HDAC1 was overexpressed in RA synovial tissues as well as in IL-17- stimulated synoviocytes by. The inhibitor of HADC1, TSA, but not NAM, could enhanc the expression of IL-17- induced Cyr61 in synoviocytes. But this effect of enhancement was offset by PDTC. This study has illuminated that HDAC1 plays an important role in the expression of IL-17- induced Cry61 in synovial cells and the mechanism may be correlated with regulation of NF-κB activity.