Il-34 regulates MAPKs, PI3K/Akt, JAK and NF-κB pathways and induces the expression of inflammatory factors in RA-FLS
Il-34 regulates MAPKs, PI3K/Akt, JAK and NF-κB pathways and induces the expression of inflammatory factors in RA-FLS
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Il-34 调节 MAPK、PI3K/Akt、JAK 和 NF-κB 通路并诱导 RA-FLS 中炎症因子的表达
DOI：
10.55563/clinexprheumatol/6t1d4i
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Xiaofei Lai
中科院分区：
文献类型：
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作者：
Huiqing Yang;Yan Luo;Xiaofei Lai
目的：目的探讨白细胞介素34（IL-34）在类风湿关节炎（RA）中的作用及其相关信号通路，以及IL-34在胶原诱导关节炎（CIA）模型小鼠中的表达水平。方法：用纯化的IL-34刺激培养的RA成纤维样滑膜细胞（RA FLS）。采用酶联免疫吸附试验（ELISA）检测炎症细胞因子的表达水平，采用蛋白质印迹试验（WB）检测磷酸化信号分子的水平。建立CIA模型后，检测小鼠足指数和血清IL-34表达水平。结果如下：IL-34显著增加IL-8和TNF-α的分泌，但对IL-6无显著影响，且这种作用可被信号抑制剂削弱。同时，IL-34激活了多种信号通路，而用抑制剂处理可以降低磷酸化强度。在动物实验中，模型组小鼠体重减轻，爪子明显肿胀、溃烂，甚至僵硬。滑膜组织增生，大量炎性细胞浸润，骨和软骨破坏，形成典型的血管翳。结论：IL-34可通过MAPK、PI 3 K/Akt、JAK和NF-κB信号通路介导RA-FLS细胞产生和分泌IL-8和TNF-α，同时上调胶原诱导关节炎小鼠血清IL-34的表达。
Objectives: To explore the role of interleukin 34 (IL-34) in rheumatoid arthritis (RA) and its related signalling pathways as well as the expression levels of IL-34 in collagen-induced arthritis (CIA) modelling mice...Methods: Recombination IL-34 was used to stimulate cultured RA fibroblast-like synoviocytes (RA-FLS). The expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA), and the levels of phosphorylation signalling molecules were detected by western blotting assay (WB). After the establishment of the CIA model, paw indexes and serum IL-34 expression levels of mice were evaluated...Results: IL-34 significantly increased the secretion of IL-8 and TNF-α but had no significant effect on IL-6, and this effect could be impaired by signal inhibitors. At the same time, IL-34 activated multiple signalling pathways, whereas treating with inhibitors could reduce phosphorylation intensity. In animal experiments, mice in the model group had lost weight, and their paws were obviously swollen, ulcerous, and even stiffened. The hyperplasia of synovial tissue, infiltration of many inflammatory cells, and destruction of bone and cartilage from the typical pannus formation were also apparently observed...Conclusions: IL-34 can mediate the production and secretion of IL-8 and TNF-α in RA-FLS cells through MAPKs, PI3K/Akt, JAK and NF-κB signalling pathways, while the expression of serum IL-34 in collagen-induced arthritis mice is also upregulated.