银屑病关节炎Dicer mRNA低表达对TNF-ɑ、IL-6表达的影响

Effect of downregulation of dicer mRNA expression on TNF-ɑand IL-6 in psoriatic arthritis

目的在银屑病关节炎(PsA)患者中检测Dicer mRNA的表达,分析Dicer mRNA表达及与PsA临床特征的相关性,探讨Dicer在PsA发病机制中的作用。方法收集分离30例PsA患者和25例健康对照者外周血单核细胞(PBMCs),采用实时荧光定量聚合酶链反应检测PBMCs中Dicer mRNA的表达。通过DAPSA评估PsA患者的疾病活动度。通过细胞转染和刺激研究Dicer在PBMCs中的生物功能。采用酶联免疫法检测Dicer对肿瘤坏死因子ɑ(TNF-ɑ)、IL-6表达的影响。结果PsA患者PBMCs中Dicer mRNA表达水平较健康对照组显著降低(P=0.0014),PsA患者PBMCs中的Dicer mRNA表达水平与PsA患者的DAPSA评分呈负相关(r=-0.5181,P=0.0034)。LPS刺激后,PsA患者PBMCs可以分泌更高水平的TNF-ɑ和IL-6,转染Dicer小干扰RNA的PBMCs亦可以升高TNF-ɑ和IL-6蛋白表达。结论Dicer mRNA在PsA患者中表达降低。Dicer mRNA表达与PsA疾病的活动相关,可以作为PsA活动性指标。改变Dicer可以调控TNF-ɑ、IL-6的表达,提示Dicer对PsA患者炎症细胞因子TNF-ɑ、IL-6起到重要的调控作用。

Objective To detect the expression of Dicer mRNA in peripheral blood mononuclear cells(PBMCs)in patients with psoriatic arthritis(PsA)and explore the role of Dicer in pathogenesis of PsA.Methods PBMCs were obtained and isolated from 30 patients with PsA and 25 healthy controls.Reverse transcription-polymerase chain reaction(RT-PCR)was used to test Dicer mRNA expression in PBMCs.Disease activity of PsA was assessed by Disease Activity index for Psoriatic Arthritis(DAPSA).The biological function of Dicer in PBMCs was studied by cell transfection and stimulation.The expression of tumor necrosis factor(TNF)-ɑand IL-6 was assessed by ELISA.Results The expression of Dicer mRNA was downregulated in PBMCs in PsA groups when compared to healthy controls(P=0.0014).The Dicer mRNA expression levels negatively correlated with DAPSA scores(r=-0.5181,P=0.0034).PBMCs from PsA could secrete higher levels of TNF-ɑand IL-6 in response to LPS.Transfection of Dicer siRNA increased TNF-ɑand IL-6 expression at the protein levels.Conclusions Dicer mRNA expression was downregulated in PsA patients.Dicer mRNA expression was negatively correlated with DAPSA.The expression of Dicer mRNA can be used as a marker of PsA activity.Manipulating the expression of Dicer can regulate the expression of TNF-αand IL-6.These results suggest that Dicer may play an important regulatory role in inflammatory cytokine TNF-ɑand IL-6 in PsA patients.