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白细胞介素-9促进人退变椎间盘组织中肿瘤坏死因子-α和前列腺素E2的释放。

Interleukin-9 Promotes TNF-α and PGE2 Release in Human Degenerated Intervertebral Disc Tissues.

作者信息

Zhang Yuanqiang, Zhao Yunpeng, Li Jingkun, Wang Shuaishuai, Liu Yi, Nie Lin, Cheng Lei

机构信息

Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong, China.

出版信息

Spine (Phila Pa 1976). 2016 Nov 1;41(21):1631-1640. doi: 10.1097/BRS.0000000000001621.

DOI:10.1097/BRS.0000000000001621
PMID:27802252
Abstract

STUDY DESIGN

Based on human disc surgical samples and isolated cells in vitro, we undertook a descriptive and mechanistic investigation of proinflammatory effects of interleukin (IL)-9 in intervertebral disc (IVD) degeneration.

OBJECTIVE

To investigate the proinflammatory role of IL-9 in the pathological process of IVD degeneration.

SUMMARY OF BACKGROUND DATA

IL-9 is known as a pleiotropic cytokine that regulates the human pathogenesis of inflammatory and autoimmune diseases. However, whether IL-9 cytokine is involved in the immuno-inflammatory pathogenesis of IVD degeneration is unclear.

METHODS

The IVD samples were obtained from 45 patients. Immunohistochemistry, western blot, and real-time Polymerase Chain Reaction (PCR) were performed to detect the expression of IL-9 and tumor necrosis factor alpha (TNF-α) in the degenerated IVDs. Moreover, nucleus pulposus (NP) cells were treated with 0, 1, 10, and 100 ng/mL IL-9 cytokine and stimulated with IL-9 alone at 100 ng/mL for 0, 12, 24, and 48 hours. TNF-α expression was determined by immunofluorescence staining, western blot, and real-time PCR, respectively. The amounts of TNF-α and prostaglandin E2 (PGE2) in the supernatant were quantified by enzyme-linked immunosorbent assay. Additionally, Spearman correlation analyses were performed to analyze the correlation between Pfirrmann grading score of the involved degenerated IVDs and serum levels of IL-9.

RESULTS

The expressions of IL-9 and TNF-α in degenerated IVD tissues were dramatically elevated in comparison with the control. IL-9 significantly up-regulated the TNF-α and PGE2 secretion of NP cells in dose- and time-dependent manner. Moreover, there is a positive correlation between IL-9 serum level and severity of involved IVD degeneration.

CONCLUSION

Our findings suggest that IL-9 may play a potential role in the inflammatory processes of IVD degeneration. IL-9 may be involved in the IVD degeneration, at least in part, though stimulating the release of TNF-α and PGE2 in NP cells.

LEVEL OF EVIDENCE

N/A.

摘要

研究设计

基于人体椎间盘手术样本和体外分离细胞,我们对白细胞介素(IL)-9在椎间盘(IVD)退变中的促炎作用进行了描述性和机制性研究。

目的

研究IL-9在IVD退变病理过程中的促炎作用。

背景数据总结

IL-9是一种多效性细胞因子,可调节人类炎症和自身免疫性疾病的发病机制。然而,IL-9细胞因子是否参与IVD退变的免疫炎症发病机制尚不清楚。

方法

从45例患者中获取IVD样本。采用免疫组织化学、蛋白质免疫印迹和实时聚合酶链反应(PCR)检测退变IVD中IL-9和肿瘤坏死因子α(TNF-α)的表达。此外,将髓核(NP)细胞分别用0、1、10和100 ng/mL的IL-9细胞因子处理,并单独用100 ng/mL的IL-9刺激0、12、24和48小时。分别通过免疫荧光染色、蛋白质免疫印迹和实时PCR测定TNF-α的表达。通过酶联免疫吸附测定法定量上清液中TNF-α和前列腺素E2(PGE2)的含量。此外,进行Spearman相关性分析,以分析受累退变IVD的Pfirrmann分级评分与血清IL-9水平之间的相关性。

结果

与对照组相比,退变IVD组织中IL-9和TNF-α的表达显著升高。IL-9以剂量和时间依赖性方式显著上调NP细胞的TNF-α和PGE2分泌。此外,IL-9血清水平与受累IVD退变的严重程度呈正相关。

结论

我们的研究结果表明,IL-9可能在IVD退变的炎症过程中发挥潜在作用。IL-9可能至少部分通过刺激NP细胞释放TNF-α和PGE2而参与IVD退变。

证据水平

无。

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