Li Qiang, Guo Hongjun, Li Huihui, Zhu Qi, Liu Yang
Pharmazie. 2017 May 1;72(5):260-264. doi: 10.1691/ph.2017.6904.
In various tumors, aberrant expression of P54/nrb has been identified. However, the expression pattern and specific role of P54/nrb in rheumatoid arthritis (RA) has never been explored. Here, we first demonstrated that the expression of P54/nrb was markedly enhanced in the synovial tissues of RA patients. Functional study showed that P54/nrb could enhance the levels of inflammatory factors, including IL-1, IL-2, IL-6, IL-8 and TNFα. More importantly, we first found that overexpression of P54/nrb can induce the protein levels of P65, an important subunit of NF-κB. In contrast, knockdown of P54/nrb by RNAi significantly decreased the expression of NF-κB. Luciferase reporter assay and CHIP assay showed that P54/nrb could transcriptionally activate the expression of NF-κB, thereby enhancing pro-inflammatory responses. In summary, the expression of p54 was markedly increased in the synovial tissues of RA patients. Further study demonstrated that p54 could transcriptionally activate the expression of p65, an important NF-κB subunit, thereby enhancing the pro-inflammatory response.
在多种肿瘤中，已发现P54/nrb存在异常表达。然而，P54/nrb在类风湿关节炎（RA）中的表达模式及具体作用尚未得到研究。在此，我们首先证明RA患者滑膜组织中P54/nrb的表达显著增强。功能研究表明，P54/nrb可提高包括IL-1、IL-2、IL-6、IL-8和TNFα在内的炎症因子水平。更重要的是，我们首次发现P54/nrb的过表达可诱导NF-κB重要亚基P65的蛋白水平升高。相反，通过RNAi敲低P54/nrb可显著降低NF-κB的表达。荧光素酶报告基因检测和染色质免疫沉淀检测表明，P54/nrb可转录激活NF-κB的表达，从而增强促炎反应。总之，RA患者滑膜组织中p54的表达显著增加。进一步研究表明，p54可转录激活NF-κB重要亚基p65的表达，从而增强促炎反应。
