背景:信号素是参与神经发育的轴突引导分子,有助于调节免疫反应的各个阶段。本研究旨在探讨促炎细胞因子白细胞介素-6(IL-6)和调节性T细胞相关细胞因子白细胞介素-10(IL-10)的血浆水平,以及叉头盒P3(FoxP3)的基因表达水平,信号3A(Sema-3A),Neuropilin-1(Nrp-1),信号-4A(Sema-4A),和Plexin-D1(Plxn-D1),与健康对照组相比,接受常规疾病缓解抗风湿药(DMARDs)治疗6个月的新诊断的类风湿关节炎(RA)患者的外周血中。
方法:从40例新诊断的RA患者(治疗前后)和40例年龄和性别匹配的健康受试者中采集外周血样本。通过酶联免疫吸附试验(ELISA)定量血浆IL-6和IL-10的浓度,和FoxP3,Sema-3A的mRNA表达水平,Nrp-1,Sema-4A,和Plxn-D1通过定量实时PCR评估。
结果:与对照组相比,RA患者(治疗前和治疗后)的血浆IL-6水平显著升高(P<0.001).与预处理水平相比,DMARD治疗后血浆IL-6水平显著降低(P<0.05)。此外,治疗后RA患者血浆IL-10水平明显高于对照组(P<0.05)。FoxP3、Sema-3A、治疗前RA患者的Nrp-1显著低于对照组(P<0.001)。与治疗前的RA患者相比,FoxP3,Sema-3A,在DMARDs治疗的RA患者中,Nrp-1明显升高(分别为P<0.05,P<0.01和P<0.01)。Sema-3A基因表达与FoxP3基因表达呈正相关(r=0.292,P<0.01),Nrp-1基因表达呈正相关(r=0.569,P<0.0001)。
结论:常规DMARDs治疗可通过增加FoxP3、Sema-3A、和Nrp-1基因表达。
BACKGROUND: Semaphorins are axonal guidance molecules involved in neural development and contribute to the regulation of various phases of the immune response. This study aimed to investigate the plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and the regulatory T (Treg) cell-related cytokine interleukin-10 (IL-10), as well as the gene expression levels of forkhead box P3 (
FoxP3), Semaphorin-3A (Sema-3A), Neuropilin-1 (Nrp-1), Semaphorin-4A (Sema-4A), and Plexin-D1 (Plxn-D1), in the peripheral blood of newly diagnosed rheumatoid arthritis (RA) patients treated with conventional disease-modifying antirheumatic drugs (DMARDs) for 6 months compared with healthy controls.
METHODS: Peripheral blood samples were obtained from 40 newly diagnosed RA patients (before and after treatment) and 40 age- and sex-matched healthy subjects. The plasma concentrations of IL-6 and IL-10 were quantified via enzyme-linked immunosorbent assay (ELISA), and the mRNA expression levels of
FoxP3, Sema-3A, Nrp-1, Sema-4A, and Plxn-D1 were assessed via quantitative real-time PCR.
RESULTS: Compared with those in the controls, the plasma IL-6 levels in the RA patients (both pre- and post-treatment) were significantly greater (P < 0.001). Compared with the pre-treatment levels, the plasma IL-6 levels decreased significantly after DMARD therapy (P < 0.05). Moreover, plasma IL-10 levels were significantly greater in post-treatment RA patients than in controls (P < 0.05). The gene expression of
FoxP3, Sema-3A, and Nrp-1 was significantly lower in pre-treated RA patients than in controls (P < 0.001). Compared with that in pre-treatment RA patients, the gene expression of
FoxP3, Sema-3A, and Nrp-1 in DMARDs-treated RA patients was strongly increased (P < 0.05, P < 0.01, and P < 0.01, respectively). There was a positive correlation between Sema-3A gene expression and the gene expression of
FoxP3 (r = 0.292, P < 0.01) and Nrp-1 (r = 0.569, P < 0.0001).
CONCLUSIONS: Conventional DMARDs therapy effectively reduces disease activity and inflammation in newly diagnosed RA patients by increasing FoxP3, Sema-3A, and Nrp-1 gene expression.