Blocking the function of inflammatory cytokines and mediators by using IL-10 and TGF-β: a potential biological immunotherapy for intervertebral disc degeneration in a beagle model.

Blocking the function of inflammatory cytokines and mediators by using IL-10 and TGF-β: a potential biological immunotherapy for intervertebral disc degeneration in a beagle model.
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使用 IL-10 和 TGF-β 阻断炎症细胞因子和介质的功能:Beagle 模型中椎间盘退变的潜在生物免疫疗法

DOI:
10.3390/ijms151017270
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发表时间:
2014-09-26
影响因子:
5.6
通讯作者:
Ruan D
Ruan D
中科院分区:
生物学2区
文献类型:
--
作者:
Li W;Liu T;Wu L;Chen C;Jia Z;Bai X;Ruan D

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腰痛的衰弱效应是世界范围内的一个主要健康问题。多种因素导致这种情况,通常椎间盘退变(IDD)是这种疾病的潜在原因。炎症有助于IDD的发生,炎症因子如肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β在IDD的病理中起关键作用。因此,在IDD患者中开发抑制TNF-α和IL-1β表达和/或作用的治疗方法应该是一种有前景的治疗方法。本研究表明,在犬IDD模型中,IL-10和TGF-β治疗可能抑制退行性椎间盘(NP)细胞中炎症细胞因子的产生。通过手术诱导6只雄性比格犬的IDD,分离并培养退行性NP细胞,用于体外研究细胞因子的产生。将培养的退行性NP细胞分为4个实验组:未处理对照组、IL-10处理组、TGF-β处理组、IL-10 + TGF-β处理组。以正常培养的NP细胞为对照组。采用荧光活化细胞分选(FACS)和酶联免疫吸附法(ELISA)检测TNF-α的表达;ELISA和real-time PCR检测IL-10和TGF-β对NP细胞细胞因子表达的影响。我们的结果表明,IL-10和TGF-β治疗抑制IL-1β和TNF-α的表达,抑制炎症反应的发生。这些数据表明,IL-10和TGF-β应作为治疗IDD介导的下背部疼痛的治疗方法。
The debilitating effects of lower back pain are a major health issue worldwide. A variety of factors contribute to this, and oftentimes intervertebral disk degeneration (IDD) is an underlying cause of this disorder. Inflammation contributes to IDD, and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, play key roles in the pathology of IDD. Therefore, the development of treatments that inhibit the expression and/or effects of TNF-α and IL-1β in IDD patients should be a promising therapeutic approach to consider. This study characterized the potential to suppress inflammatory cytokine production in degenerative intervertebral disc (NP) cells by treatment with IL-10 and TGF-β in a canine model of IDD. IDD was induced surgically in six male beagles, and degenerative NP cells were isolated and cultured for in vitro studies on cytokine production. Cultured degenerative NP cells were divided into four experimental treatment groups: untreated control, IL-10-treated, TGF-β-treated, and IL-10- plus TGF-β-treated cells. Cultured normal NP cells served as a control group. TNF-α expression was evaluated by fluorescence activated cell sorting (FACS) analysis and enzyme-linked immunosorbent assay (ELISA); moreover, ELISA and real-time PCR were also performed to evaluate the effect of IL-10 and TGF-β on NP cell cytokine expression in vitro. Our results demonstrated that IL-10 and TGF-β treatment suppressed the expression of IL-1β and TNF-α and inhibited the development of inflammatory responses. These data suggest that IL-10 and TGF-β should be evaluated as therapeutic approaches for the treatment of lower back pain mediated by IDD.
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