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促炎趋化因子 RANTES/CCL5 和细胞因子 IL-1β 在人类痛性椎间盘组织中的表达及相关性研究。

Expression and relationship of proinflammatory chemokine RANTES/CCL5 and cytokine IL-1β in painful human intervertebral discs.

机构信息

Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA.

出版信息

Spine (Phila Pa 1976). 2013 May 15;38(11):873-80. doi: 10.1097/BRS.0b013e318285ae08.

DOI:10.1097/BRS.0b013e318285ae08
PMID:23660804
Abstract

STUDY DESIGN

Laboratory study.

OBJECTIVE

To evaluate expression of chemokine regulated and normal T cell expressed and secreted (RANTES)/C-C motif ligand 5 (CCL5) and interleukins in intervertebral discs (IVDs) specimens from patients with discogram-proven painful degeneration.

SUMMARY OF BACKGROUND DATA

Discogenic back pain results in tremendous costs related to treatment and lost productivity. The relationship between inflammation, degeneration (IVD), and cytokine upregulation is well established, but other mediators of the inflammatory cascade are not well characterized.

METHODS

Painful IVDs were taken from 18 patients undergoing surgery for discogenic pain with positive preoperative discogram. Painless control tissue was taken at autopsy from patients without back pain/spinal pathology or spinal levels with negative discograms resected for deformity.Quantitative real time polymerase chain reaction (qRT-PCR) was performed to evaluate RANTES, IL-1β, IL-6, and IL-8 expression in painful and control discs. RANTES and interleukin expression were analyzed on the basis of Pfirrmann grade.Disc cells were cultured in alginate beads using 2 groups: an untreated group and a group treated with 10 ng/mL IL-1β, 10 ng/mL TNF-α, and 1% fetal bovine serum to induce a degenerative phenotype.

RESULTS

Nine painless IVD specimens and 7 painful IVD specimens were collected. RANTES expression demonstrated a 3.60-fold increase in painful discs versus painless discs, a significant difference (P = 0.049). IL-1β expression demonstrated significantly higher expression in painful discs (P = 0.03). RANTES expression data demonstrated significant upregulation with increasing Pfirrmann grade (P = 0.045). RANTES expression correlated significantly with IL-1β expression (ρ = 0.67, P < 0.0001). RANTES expression increased more than 200-fold in the alginate culture model in cells treated with IL-1β/TNF-α, 1% fetal bovine serum (P < 0.001).

CONCLUSION

RANTES and IL-1β expression was significantly elevated in painful IVDs after careful selection of painless versus painful IVD tissue. RANTES expression was found to correlate significantly with expression of IL-1β. RANTES was upregulated by IL-1β/TNF-α/1% fetal bovine serum an in vitro treatment to induce a degenerative phenotype.

摘要

研究设计

实验室研究。

目的

评估在椎间盘造影术证实有疼痛性退变的患者的椎间盘标本中趋化因子调节正常 T 细胞表达和分泌(RANTES)/C-C 基序配体 5(CCL5)和白细胞介素的表达。

背景资料概要

椎间盘源性腰痛导致与治疗和生产力损失相关的巨大费用。炎症、退变(IVD)和细胞因子上调之间的关系已经得到很好的证实,但炎症级联的其他介质尚未得到很好的描述。

方法

对 18 例因椎间盘造影术阳性而行手术治疗椎间盘源性疼痛的患者进行手术,获取疼痛性椎间盘。在无腰痛/脊柱病理学或行脊柱融合术的阴性椎间盘造影术切除的脊柱水平进行尸检,获取无痛对照组织。采用实时定量聚合酶链反应(qRT-PCR)评估疼痛性和对照椎间盘中 RANTES、IL-1β、IL-6 和 IL-8 的表达。根据 Pfirrmann 分级分析 RANTES 和白细胞介素的表达。将椎间盘细胞在藻酸盐珠中培养,分为两组:未经处理组和用 10ng/mlIL-1β、10ng/mlTNF-α和 1%胎牛血清处理的组,以诱导退行性表型。

结果

收集了 9 例无痛椎间盘标本和 7 例疼痛性椎间盘标本。疼痛性椎间盘中 RANTES 的表达与无痛椎间盘相比增加了 3.60 倍,差异有统计学意义(P=0.049)。疼痛性椎间盘中 IL-1β 的表达显著升高(P=0.03)。RANTES 表达数据显示 Pfirrmann 分级越高,表达上调越显著(P=0.045)。RANTES 表达与 IL-1β 表达呈显著正相关(ρ=0.67,P<0.0001)。在 IL-1β/TNF-α、1%胎牛血清处理的藻酸盐培养模型中,RANTES 的表达增加了 200 多倍(P<0.001)。

结论

在仔细选择疼痛性与无痛性椎间盘组织后,在疼痛性椎间盘组织中 RANTES 和 IL-1β 的表达明显升高。RANTES 表达与 IL-1β 表达呈显著正相关。在 IL-1β/TNF-α/1%胎牛血清诱导的退行性表型中,RANTES 被上调。

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