IL-37 通过 IL-1R8/NF-κB 通路缓解椎间盘退变。
IL-37 alleviates intervertebral disc degeneration via the IL-1R8/NF-κB pathway.
机构信息
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
出版信息
Osteoarthritis Cartilage. 2023 May;31(5):588-599. doi: 10.1016/j.joca.2023.01.006. Epub 2023 Jan 21.
OBJECTIVE
Intervertebral disc degeneration (IDD) has been reported to be a major cause of low back pain (LBP). Interleukin (IL)-37 is an anti-inflammatory cytokine of the interleukin-1 family, which exerts salutary physiological effects. In this study, we assessed the protective effect of IL-37 on IDD progression and its underlying mechanisms.
METHODS
Immunofluorescence (IF) was conducted to measure IL-37 expression in nucleus pulposus tissues. CCK-8 assay and Edu staining were used to examine the vitality of IL-37-treated nucleus pulposus cells (NPCs). Western blot, qPCR, ELISA as well as immunohistochemistry were used to assess senescence associated secreted phenotype (SASP) factors expression; and NF-κB pathway was evaluated by western blot and IF; while IL-1R8 knock-down by siRNAs was performed to ascertain its significance in the senescence phenotype modulated by IL-37. The therapeutic effect of IL-37 on IDD were evaluated in puncture-induced rat model using X-ray, Hematoxylin-Eosin, Safranin O-Fast Green (SO), and alcian blue staining.
RESULTS
We found IL-37 expression decreased in the IDD process. In vitro, IL-37 suppressed SASP factors level and senescence phenotype in IL-1β treated NPCs. In vivo, IL-37 alleviated the IDD progression in the puncture-induced rat model. Mechanistic studies demonstrated that IL-37 inhibited IDD progression by downregulating NF-κB pathway activation in NPCs by activating IL-1R8.
CONCLUSION
The present study suggests that IL-37 delays the IDD development through the IL-1R8/NF-κB pathway, which suggests IL-37 as a promising novel target for IDD therapy.
目的
椎间盘退行性变（IDD）已被报道为腰痛（LBP）的主要原因。白细胞介素（IL）-37 是白细胞介素 1 家族的抗炎细胞因子，具有有益的生理作用。在本研究中，我们评估了 IL-37 对 IDD 进展的保护作用及其潜在机制。
方法
免疫荧光（IF）用于测量核髓核组织中 IL-37 的表达。CCK-8 测定和 Edu 染色用于检测 IL-37 处理的核髓核细胞（NPC）的活力。Western blot、qPCR、ELISA 和免疫组织化学用于评估衰老相关分泌表型（SASP）因子的表达；通过 Western blot 和 IF 评估 NF-κB 途径；通过 siRNAs 敲低 IL-1R8 以确定其在 IL-37 调节的衰老表型中的意义。使用 X 射线、苏木精-伊红、番红 O-快绿（SO）和阿利新蓝染色评估 IL-37 对穿刺诱导的大鼠模型中 IDD 的治疗效果。
结果
我们发现 IL-37 在 IDD 过程中的表达降低。在体外，IL-37 抑制了 IL-1β 处理的 NPC 中的 SASP 因子水平和衰老表型。在体内，IL-37 减轻了穿刺诱导的大鼠模型中的 IDD 进展。机制研究表明，IL-37 通过激活 IL-1R8 抑制 NPC 中 NF-κB 途径的激活，从而抑制 IDD 的进展。
结论
本研究表明，IL-37 通过 IL-1R8/NF-κB 途径延迟 IDD 的发展，这表明 IL-37 是 IDD 治疗的一个有前途的新靶点。
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