1st Affiliated Hospital of China Medical University, Department of Rheumatology, Shen Yang, 110001, China.
1st Affiliated Hospital of China Medical University, Department of Rheumatology, Shen Yang, 110001, China, Department of Rheumatology, 1st Affiliated Hospital of Jinzhou Medical University, Jin Zhou, China, 121000.
Eur Cytokine Netw. 2019 Jun 1;30(2):67-73. doi: 10.1684/ecn.2019.0428.
To detect the effect of interleukin (IL)-34 on the secretion of Receptor activator of nuclear factor kappa-B ligand (RANKL)/Osteoprotegerin (OPG) and Matrix metalloproteinase (MMP)-3 by fibroblast-like synoviocytes (FLS) and peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and to investigate whether the effect is mediated by IL-17.
RA-FLS and RA-PBMCs were stimulated with recombinant human (rh) IL-34, with or without the IL-17 inhibitor Plumbagin. The supernatant of the culture medium was collected and the levels of RANKL, OPG, and MMP-3 were detected by enzyme-linked immunosorbent assay (ELISA).
RhIL-34 promoted RANKL secretion and inhibited OPG secretion in RA-FLS. The effect was weakened by the addition of the IL-17 inhibitor. In contrast, rhIL-34 had no significant effect on MMP-3 secretion by FLS. RhIL-34 elevated the secretion of RANKL by RA-PBMCs but not by healthy-PBMCs. Furthermore, the secretion of RANKL by RA-PBMCs reduced after the addition of the IL-17 inhibitor. OPG secretion by both RA-FLS and FLS from healthy controls was inhibited by rhIL-34, but were elevated after the addition of the IL-17 inhibitor. RhIL-34 had no significant effect on MMP-3 secretion by both RA-PBMCs and healthy-PBMCs.
IL-34 enhances RANKL/OPG expression by RA-FLS and RA-PBMCs, and this effect is, indirectly, mediated by IL-17. This cytokine is therefore likely to to play an important role in local joint destruction and systemic osteoporosis in RA, and is therefore a potential therapeutic target for the treatment of this disease.
检测白细胞介素 (IL)-34 对类风湿关节炎 (RA) 患者成纤维样滑膜细胞 (FLS) 和外周血单个核细胞 (PBMC) 分泌核因子 κB 受体激活剂配体 (RANKL)/骨保护素 (OPG) 和基质金属蛋白酶 (MMP)-3 的影响，并探讨其是否通过白细胞介素 17 (IL-17) 介导。
用重组人 (rh) IL-34 刺激 RA-FLS 和 RA-PBMC，同时加入 IL-17 抑制剂 Plumbagin。收集培养上清液，用酶联免疫吸附试验 (ELISA) 检测 RANKL、OPG 和 MMP-3 的水平。
rhIL-34 促进 RA-FLS 中 RANKL 的分泌，抑制 OPG 的分泌。加入 IL-17 抑制剂后，作用减弱。相反，rhIL-34 对 FLS 中 MMP-3 的分泌无显著影响。rhIL-34 可升高 RA-PBMC 中 RANKL 的分泌，但对健康人 PBMC 无明显作用。此外，加入 IL-17 抑制剂后，RA-PBMC 中 RANKL 的分泌减少。rhIL-34 抑制 RA-FLS 和健康对照 FLS 中 OPG 的分泌，但加入 IL-17 抑制剂后 OPG 的分泌增加。rhIL-34 对 RA-PBMC 和健康人 PBMC 中 MMP-3 的分泌均无明显影响。
IL-34 增强 RA-FLS 和 RA-PBMC 中 RANKL/OPG 的表达，这种作用间接通过 IL-17 介导。因此，该细胞因子可能在 RA 局部关节破坏和全身骨质疏松症中发挥重要作用，是治疗该疾病的潜在治疗靶点。
