Department of Rheumatology, the First Hospital of China Medical University, Shenyang, China.
Department of Rheumatology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Immunol Invest. 2020 Feb;49(1-2):81-87. doi: 10.1080/08820139.2019.1649281. Epub 2019 Aug 12.
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.
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).
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.
IL-34 may indirectly contribute to angiogenesis by promoting the production of VEGF and HIF-1α and participate in the pathogenesis of RA.
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。
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。
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。
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。
