ABSTRACT
BACKGROUND:The etiological factor for rheumatoid arthritis remains unclear, but the effects of nuclear factor-κB on the onset of rheumatoid arthritis have been gradual y paid great attention by rheumatologists. OBJECTIVE:By using the RNA interference (RNAi) technique to block the signal pathway of nuclear factor-κB mRNA of human rheumatoid arthritis synovial cells, this study explored its application prospect in the treatment of rheumatoid arthritis. METHODS:The synovial cells were isolated, digested, and cultured for further use. In accordance with the design principle of smal interfering RNA (siRNA), target sequences of siRNA of nuclear factor-κB were identified, and siRNA expression vector of nuclear factor-κB was synthesized and constructed. The four pGenesil-1/nuclear factor-κB siRNA expression vectors were transfected into the first passage of synovial cells that wel grew. Blank and negative control groups were set. cells at 12, 24, 48, 72 hours, 5 and 7 days after transfection were col ected, and RNA was extracted. Intracellular nuclear factor-κB mRNA expression levels were measured, and siRNA plasmid vector that could effectively inhibit nuclear factor-κB mRNA expression was screened out. RESULTS AND CONCLUSION:Nuclear factor-κB highly expressed in synovial cells after human rheumatoid arthritis. 3#pGenesil-1/nuclear factor-κB apparently suppressed nuclear factor-κB mRNA expression in synovial cells with human rheumatoid arthritis. RNAi technique blocked nuclear factor-κB mRNA expression. Therefore, the block of nuclear factor-κB signal pathway might be a good target for rheumatoid arthritis gene therapy.
ABSTRACT
BACKGROUND:Nuclear transcription factor(NTF) ?B is a transcription factor,which exists universally in eukaryocyte.It has been identified that its overacting is correlated to the ongoing and development of many diseases.Among the pathomechanism of rheumatoid arthritis,the abnormal activation of NTF ?B has a lot to do with the inflammatory hyperplasia of synovium and the erosion of tissue around articulation.OBJECTIVE:To review the recent progress of NTF ?B,pathogenesis and treatment of rheumatoid arthritis.RETRIEVAL STRATEGY:A computer-based online search of PubMed database was undertaken to identify the articles published in English from January 2000 to July 2007,with the Key words of "nuclear transcription factor ?B,rheumatoid arthritis,pathogenesis,treatment".Meanwhile,Wanfang database was searched for the related Chinese articles published between January 2000 and July 2007,with the same key words in Chinese.A total of 72 articles were finally selected for the first trial.Inclusive criteria:the articles focus on the NTF ?B,the pathogenesis and treatment of rheumatoid arthritis.Exclusive criteria:repeated experiments.LITERATURE EVALUATION:Among the 30 inclusive literatures,7 were related to reviews while the others were clinical or basic researches.DATA SYNTHESIS:①NTF ?B is a significant transcription factor,which participates in regulating many genes related to immune function and inflammation reaction.The promoters of many genes have the binding sites of NTF ?B.②It is indicated that the abnormal activation of NTF ?B plays an important role in the pathogenesis of rheumatoid arthritis.In recent years,many researches inhibiting its activation through different components of signaling pathways have been doing,which become very hot in anti-inflammatory and anti-rheumatism treatment.③In recent years,people have been making great progress in the therapy of rheumatoid arthritis aiming at cytokine and its receptor,however,interfering NTF ?B to treat rheumatoid arthritis is still in study stage.CONCLUSION:NTF ?B target therapy provides a new therapeutic strategy for the treatment of rheumatoid arthritis,which is a very exciting prospect indeed.