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白细胞介素-34 对类风湿关节炎患者外周血单个核细胞分泌血管生成细胞因子的影响。

Effect of Interleukin-34 on Secretion of Angiogenesis Cytokines by Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis.

机构信息

Department of Rheumatology, the First Hospital of China Medical University, Shenyang, China.

Department of Rheumatology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

出版信息

Immunol Invest. 2020 Feb;49(1-2):81-87. doi: 10.1080/08820139.2019.1649281. Epub 2019 Aug 12.

Abstract

BACKGROUND

Interleukin (IL)-34 is a new pro-inflammatory cytokine. Previous studies showed that IL-34 plays a key role in inflammation and osteoporosis in rheumatoid arthritis (RA). However, whether IL-34 participates in angiogenesis in RA remains unknown. Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) play critical roles in the angiogenesis of RA.

METHODS

22 patients with RA, 18 patients with ankylosing spondylitis (AS), and 8 healthy subjects were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and purified from peripheral blood by density gradient centrifugation. PBMCs were stimulated using anti-CD3/CD28 antibody and different concentrations of recombinant human (rh) IL-34 (0, 10, 20, 50, 100 ng/mL). Cell-free supernatants were collected after 72 h incubation, and VEGF and HIF-1α levels were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS

IL-34 promotes the secretion of VEGF and HIF-1α by PBMCs in RA patients in a dose-dependent manner. In contrast, IL-34 has no effect on VEGF and HIF-1α secretion by PBMCs in AS and healthy controls.

CONCLUSION

IL-34 may indirectly contribute to angiogenesis by promoting the production of VEGF and HIF-1α and participate in the pathogenesis of RA.

摘要

背景

白细胞介素 (IL)-34 是一种新型促炎细胞因子。先前的研究表明,IL-34 在类风湿关节炎 (RA) 的炎症和骨质疏松中发挥关键作用。然而,IL-34 是否参与 RA 的血管生成仍不清楚。血管内皮生长因子 (VEGF) 和缺氧诱导因子-1α (HIF-1α) 在 RA 的血管生成中发挥着关键作用。

方法

本研究纳入了 22 例 RA 患者、18 例强直性脊柱炎 (AS) 患者和 8 名健康对照者。采用密度梯度离心法从外周血中分离和纯化外周血单个核细胞 (PBMC)。用抗 CD3/CD28 抗体和不同浓度的重组人 (rh) IL-34 (0、10、20、50、100 ng/mL) 刺激 PBMC。孵育 72 h 后收集无细胞上清液,采用酶联免疫吸附试验 (ELISA) 测定 VEGF 和 HIF-1α 水平。

结果

IL-34 以剂量依赖的方式促进 RA 患者 PBMC 分泌 VEGF 和 HIF-1α。相比之下,IL-34 对 AS 和健康对照组 PBMC 分泌 VEGF 和 HIF-1α 没有影响。

结论

IL-34 可能通过促进 VEGF 和 HIF-1α 的产生而间接促进血管生成,并参与 RA 的发病机制。

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