Department of Rheumatology, Clinical Medical College, Yangzhou University, Yangzhou 225000, China.
Postgraduate School, Dalian Medical University, Dalian 116000, China.
Biosci Rep. 2018 Jul 31;38(4). doi: 10.1042/BSR20180540. Print 2018 Aug 31.
Rheumatoid arthritis (RA) is a inflammatory disease that characterized with the destruction of synovial joint, which could induce disability. Inflammatory response mediated the RA. It has been reported that MiR-128-3p is significantly increased in RA, while the potential role was still unclear. T cells in peripheral blood mononuclear cell (PBMC) were isolated from the peripheral blood from people of RA and normal person were used. Real-time PCR was performed to detect the expression of MiR-128-3p, while the protein expression of tumor necrosis factor-α-induced protein 3 (TNFAIP3) was determined using Western blot. The levels of IL-6 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). The expression of CD69 and CD25 was detected using flow cytometry. The RA mouse model was constructed for verification of the role of MiR-128-3p. The expression of MiR-128-3p was significantly increased, while TNFAIP3 was decreased, the levels of IL-6 and IL-17 were also increased in the T cells of RA patients. Down-regulated MiR-128-3p significantly suppressed the expression of p-IkBα and CD69, and CD25in T cells. MiR-128-3p targets TNFAIP3 to regulate its expression. MiR-128-3p knockdown significantly suppressed the activity of nuclear factor κB (NF-κB) and T cells by up-regulating TNFAIP3, while cells co-transfected with si-TNFAIP3 abolished the effects of MiR-128-3p knockdown. The experiments verified the potential role of MiR-128-3p on RA. Down-regulated MiR-128-3p significantly suppressed the inflammation response of RA through suppressing the activity of NF-κB pathway, which was mediated by TNFAIP3.
类风湿关节炎（RA）是一种以滑膜关节破坏为特征的炎症性疾病，可导致残疾。炎症反应介导了 RA 的发生。据报道，miR-128-3p 在 RA 中显著升高，但潜在作用尚不清楚。从 RA 患者和正常人的外周血中分离外周血单个核细胞（PBMC）中的 T 细胞。实时 PCR 检测 miR-128-3p 的表达，Western blot 检测肿瘤坏死因子-α诱导蛋白 3（TNFAIP3）的蛋白表达。酶联免疫吸附试验（ELISA）测定 IL-6 和 IL-17 的水平。流式细胞术检测 CD69 和 CD25 的表达。构建 RA 小鼠模型验证 miR-128-3p 的作用。RA 患者 T 细胞中 miR-128-3p 表达明显升高，而 TNFAIP3 表达降低，IL-6 和 IL-17 水平也升高。下调 miR-128-3p 显著抑制 T 细胞中 p-IkBα 和 CD69、CD25 的表达。miR-128-3p 通过靶向 TNFAIP3 调节其表达。下调 miR-128-3p 通过上调 TNFAIP3 显著抑制 NF-κB（NF-κB）和 T 细胞的活性，而共转染 si-TNFAIP3 的细胞则消除了 miR-128-3p 下调的作用。这些实验验证了 miR-128-3p 在 RA 中的潜在作用。下调 miR-128-3p 通过抑制 NF-κB 通路的活性显著抑制 RA 的炎症反应，这是由 TNFAIP3 介导的。
