白细胞介素-19和白细胞介素-20在退变性腰椎滑脱症炎症中的作用
The roles of IL-19 and IL-20 in the inflammation of degenerative lumbar spondylolisthesis.
作者信息
Huang Kuo-Yuan, Hsu Yu-Hsiang, Chen Wei-Yu, Tsai Hui-Ling, Yan Jing-Jou, Wang Jung-Der, Liu Wen-Lung, Lin Ruey-Mo
机构信息
1Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
2Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
出版信息
J Inflamm (Lond). 2018 Sep 18;15:19. doi: 10.1186/s12950-018-0195-6. eCollection 2018.
BACKGROUND
Degenerative lumbar spondylolisthesis (DLS) is a major cause of spinal canal stenosis and is often related to lower back pain. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory bone disorders likes intervertebral disc herniation, rheumatoid arthritis (RA), osteoporosis, and bone fracture. IL-19 also acts as a proinflammatory cytokine in RA. The aim of the present study was to investigate whether IL-19 and IL-20 are involved in DLS and compare three different tissues including disc, facet joint, and ligamentum flavum of patients with DLS to verify which tissue is affected more by inflammation.
METHODS
Disc, facet joint and ligamentum flavum from 13 patients with DLS was retrieved, and the expression pattern of IL-19, IL-20, IL-20R1, IL-20R2, TNF-α, IL-1β, and MCP-1 was evaluated using immunohistochemical staining with specific antibodies. The disc cells were isolated and incubated with IL-19 and IL-20 under CoCl-mimicked hypoxic conditions to analyze the proinflammatory cytokine expression pattern using real-time quantitative PCR with specific primers.
RESULTS
IL-19 and IL-20 were positively stained and accompanied by abundant expression of TNF-α, IL-1β, and MCP-1 in facet joints of DLS patients. IL-19 and IL-20's receptors (IL-20R1 and IL-20R2) were expressed on chondrocytes and fibrocytes/fibroblasts in facet joint and ligamentum flavum tissues from patients with DLS. There was a significant correlation between the expression of IL-20 and IL-1β in facet joint. In vitro assay, IL-19 and IL-20 upregulated the expression of IL-1β, IL-6, TNF-α, IL-8, VEGF, and MCP-1 in primary cultured DLS disc cells under CoCl-mimicked hypoxic conditions.
CONCLUSIONS
IL-19, IL-20, and their receptors as well as proinflammatory cytokines (TNF-α, IL-1β, and MCP-1) were expressed more in facet joints than the other tissues in patients with DLS; therefore, the etiology of inflammation might be more facet-centric. IL-19 and IL-20 induced proinflammatory cytokine expression in disc cells and might play a role in the pathogenesis of DLS.
背景
退变性腰椎滑脱（DLS）是椎管狭窄的主要原因，常与下腰痛相关。白细胞介素-20（IL-20）正逐渐成为一种强效的血管生成、趋化和促炎细胞因子，与多种慢性炎症性骨疾病有关，如椎间盘突出症、类风湿关节炎（RA）、骨质疏松症和骨折。IL-19在RA中也作为一种促炎细胞因子发挥作用。本研究的目的是调查IL-19和IL-20是否参与DLS，并比较DLS患者的三种不同组织，即椎间盘、小关节和黄韧带，以验证哪种组织受炎症影响更大。
方法
收集13例DLS患者的椎间盘、小关节和黄韧带，使用特异性抗体进行免疫组化染色，评估IL-19、IL-20、IL-20R1、IL-20R2、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和单核细胞趋化蛋白-1（MCP-1）的表达模式。分离椎间盘细胞，在氯化钴模拟的缺氧条件下与IL-19和IL-20孵育，使用特异性引物通过实时定量PCR分析促炎细胞因子的表达模式。
结果
在DLS患者的小关节中，IL-19和IL-20呈阳性染色，并伴有TNF-α、IL-1β和MCP-1的大量表达。IL-19和IL-20的受体（IL-20R1和IL-20R2）在DLS患者小关节和黄韧带组织的软骨细胞以及纤维细胞/成纤维细胞上表达。小关节中IL-20和IL-1β的表达之间存在显著相关性。在体外实验中，在氯化钴模拟的缺氧条件下，IL-19和IL-20上调了原代培养的DLS椎间盘细胞中IL-1β、IL-6、TNF-α、IL-8、血管内皮生长因子（VEGF）和MCP-1的表达。
结论
在DLS患者中，IL-19、IL-20及其受体以及促炎细胞因子（TNF-α、IL-1β和MCP-1）在小关节中的表达高于其他组织；因此，炎症病因可能更以小关节为中心。IL-19和IL-20诱导椎间盘细胞中促炎细胞因子的表达，可能在DLS的发病机制中起作用。
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