Objective

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.

Method

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).

Results

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.

Conclusion

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.

中文翻译：

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IL-34对类风湿关节炎成纤维样滑膜细胞和外周血单个核细胞分泌RANKL/OPG的影响。

客观的

检测白细胞介素 (IL)-34 对成纤维细胞样滑膜细胞 (FLS) 和外周细胞分泌核因子 kappa-B 受体激活剂 (RANKL)/骨保护素 (OPG) 和基质金属蛋白酶 (MMP)-3 的影响类风湿性关节炎 (RA) 患者的血液单核细胞 (PBMC) 并研究该作用是否由 IL-17 介导。

方法

RA-FLS 和 RA-PBMC 用重组人 (rh) IL-34 刺激，有或没有 IL-17 抑制剂白兰素。收集培养基上清液，采用酶联免疫吸附法(ELISA)检测RANKL、OPG和MMP-3水平。

结果

RhIL-34 促进 RANKL 分泌并抑制 RA-FLS 中的 OPG 分泌。IL-17抑制剂的加入减弱了这种作用。相比之下，rhIL-34 对 FLS 的 MMP-3 分泌没有显着影响。RhIL-34 提高了 RA-PBMC 的 RANKL 分泌，但不提高健康 PBMC 的 RANKL 分泌。此外，加入 IL-17 抑制剂后，RA-PBMC 的 RANKL 分泌减少。来自健康对照的 RA-FLS 和 FLS 的 OPG 分泌被 rhIL-34 抑制，但在添加 IL-17 抑制剂后升高。RhIL-34 对 RA-PBMC 和健康 PBMC 的 MMP-3 分泌没有显着影响。

结论

IL-34 通过 RA-FLS 和 RA-PBMC 增强 RANKL/OPG 表达，并且这种作用是由 IL-17 间接介导的。因此，这种细胞因子可能在 RA 的局部关节破坏和全身性骨质疏松症中起重要作用，因此是治疗该疾病的潜在治疗靶点。