Low dose IL-2 suppress osteoclastogenesis in collagen-induced arthritis via JNK dependent pathway.
Low dose IL-2 suppress osteoclastogenesis in collagen-induced arthritis via JNK dependent pathway.
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DOI：
10.1002/iid3.364
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Sun H;Zhao Y;Wang K;Zhu L;Dong J;Zhao J;Wang Y;Li H;Sun X;Lu Y
类风湿性关节炎（RA）是最常见的慢性免疫性关节疾病之一，主要累及血管和小关节。RA复杂的发病机制大大增加了治疗的难度。目前，常用的激素和免疫抑制剂治疗效果不佳，而小剂量白细胞介素-2（IL-2）最近被发现在免疫治疗方面具有一定优势。然而，其相关的信号通路仍有待阐明。我们制作小鼠关节炎模型，然后在固定时间点注射小剂量IL-2，观察相关血管和器官病理、炎症因子和信号通路蛋白的变化，并进行统计学分析验证。低剂量IL-2可减轻胶原诱导的关节炎免疫模型中血管和骨骼病变的严重程度，并通过磷酸化核因子-κB（NF-κB）抑制体外破骨细胞形成，其抑制受体激活剂NF-κB配体作用通过c-Jun N-末端激酶（JNK）途径实现，其免疫调节作用依赖于JNK的激活。本研究首次证明低剂量IL-2可通过JNK依赖性途径抑制胶原诱导关节炎破骨细胞的形成，为今后IL-2的免疫治疗提供角度和理论依据。低剂量白细胞介素-2（IL-2）可降低胶原诱导的关节炎免疫模型中血管和骨病变的严重程度。低剂量IL-2可通过磷酸化核因子-κB（NF-κB）抑制体外破骨细胞形成，其抑制受体激活剂NF-κB配体作用通过c-Jun N-末端激酶（JNK）途径实现，其免疫调节作用依赖于JNK的激活。
Rheumatoid arthritis (RA) is one of the most common chronic immune joint diseases, mainly involving blood vessels and small joints. The complex pathogenesis of RA greatly increases the difficulty of treatment. At present, the common hormone and immunosuppressive therapy are not effective, while low‐dose interleukin‐2 (IL‐2) recently has been found to possess some advantages for immunotherapy. However, its related signal pathway remains to be elucidated. We fabricated the model of arthritis in mice, and then low‐dose IL‐2 was injected at a fixed time point to observe the changes of related vascular and organ pathology, inflammatory factors, and signal pathway proteins, which were verified by statistical analysis. Low dose IL‐2 can reduce the severity of vascular and bone lesions in collagen‐induced arthritis immune model, and inhibit osteoclast formation in vitro by phosphorylation of nuclear factor‐κB (NF‐κB), which inhibits the receptor activator of NF‐κB ligand effect through c‐Jun N‐terminal kinase (JNK) pathway, and its immunotherapeutic effect depends on the activation of JNK. It is the first time for us to prove that low dose IL‐2 can inhibit osteoclast formation in collagen‐induced arthritis through the JNK dependent pathway, which will provide the angle and theoretical basis for future immunotherapy of IL‐2. Low dose interleukin‐2 (IL‐2) can reduce the severity of vascular and bone lesions in the collagen‐induced arthritis immune model. Low dose IL‐2 can inhibit osteoclast formation in vitro by phosphorylation of nuclear factor‐κB (NF‐κB), which inhibits the receptor activator of NF‐κB ligand effect through c‐Jun N‐terminal kinase (JNK) pathway, and its immunotherapeutic effect depends on the activation of JNK.
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