Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Inflammopharmacology. 2024 Dec;32(6):3687-3695. doi: 10.1007/s10787-024-01565-1. Epub 2024 Sep 4.
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.
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.
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).
Conventional DMARDs therapy effectively reduces disease activity and inflammation in newly diagnosed RA patients by increasing FoxP3, Sema-3A, and Nrp-1 gene expression.
信号素是参与神经发育的轴突导向分子，有助于调节免疫反应的各个阶段。本研究旨在探讨新诊断的类风湿关节炎（RA）患者在接受常规疾病修饰抗风湿药物（DMARDs）治疗 6 个月后与健康对照组相比，其外周血中促炎细胞因子白细胞介素-6（IL-6）和调节性 T（Treg）细胞相关细胞因子白细胞介素-10（IL-10）的血浆水平，以及叉头框 P3（FoxP3）、信号素-3A（Sema-3A）、神经纤毛蛋白-1（Nrp-1）、信号素-4A（Sema-4A）和 Plexin-D1（Plxn-D1）的基因表达水平。
采集 40 例新诊断的 RA 患者（治疗前后）和 40 名年龄和性别匹配的健康受试者的外周血样本。采用酶联免疫吸附试验（ELISA）定量检测 IL-6 和 IL-10 的血浆浓度，采用实时定量 PCR 检测 FoxP3、Sema-3A、Nrp-1、Sema-4A 和 Plxn-D1 的 mRNA 表达水平。
与对照组相比，RA 患者（治疗前后）的血浆 IL-6 水平均显著升高（P<0.001）。与治疗前相比，DMARD 治疗后血浆 IL-6 水平显著降低（P<0.05）。此外，治疗后 RA 患者的血浆 IL-10 水平显著高于对照组（P<0.05）。与对照组相比，治疗前 RA 患者 FoxP3、Sema-3A 和 Nrp-1 的基因表达显著降低（P<0.001）。与治疗前 RA 患者相比，DMARD 治疗后的 RA 患者 FoxP3、Sema-3A 和 Nrp-1 的基因表达显著增加（P<0.05，P<0.01 和 P<0.01）。Sema-3A 基因表达与 FoxP3（r=0.292，P<0.01）和 Nrp-1（r=0.569，P<0.0001）的基因表达呈正相关。
常规 DMARDs 治疗通过增加 FoxP3、Sema-3A 和 Nrp-1 的基因表达，有效降低新诊断 RA 患者的疾病活动度和炎症。
