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多发性硬化症患者外周血单核细胞 P2X7 嘌呤能受体受醋酸格拉替雷调节。

Monocytes P2X7 purinergic receptor is modulated by glatiramer acetate in multiple sclerosis.

机构信息

Department of Medical and Occupational Sci., University of Foggia, Italy.

出版信息

J Neuroimmunol. 2012 Apr;245(1-2):93-7. doi: 10.1016/j.jneuroim.2012.02.002. Epub 2012 Feb 26.

Abstract

The aim of this study is to investigate the expression of P2X7R, IL-1beta and the ATP activity modulating ecto-apyrase CD39 on peripheral blood monocytes of MS patients and to observe the possible effects of Glatiramer Acetate (GA) on such expression. Twelve RR treatment-free MS patients were selected and peripheral blood monocytes were obtained. The expression of P2X7R, IL-1beta and CD39 on monocytes was investigated by qrt-PCR. The in vitro effects of GA on the expression of monocytes stimulated with BzATP (a potent P2X7R agonist)-were evaluated. Ten healthy donors (HDs) were similarly studied. Finally, 5 MS patients were given GA therapy and the monocytes obtained before treatment, after 3 and 12 months of GA treatment were similarly investigated. No differences were found in P2X7R, IL-1beta and CD39 expression between patients and controls. In MS Bz-ATP stimulated monocytes, GA pre-conditioning clearly downregulated P2X7R (p=0.003) but IL-1beta expression also showed a decreasing trend (p=0.07). Conversely, CD39 showed an increasing trend (p=0.07). Similar evidence was found in HDs. GA in vivo treatment induced a reduction in the expression that was clear for P2X7R and CD39 (p<0.05) but only not significant for IL-1beta after 12 months of treatment. Monocytes from both MS and control subjects express P2X7R, IL-1beta and CD39, and GA seems to interfere with such expression.

摘要

本研究旨在探讨多发性硬化症(MS)患者外周血单核细胞中 P2X7R、IL-1β 和 ATP 活性调节的外切酶 CD39 的表达,并观察 Glatiramer Acetate(GA)对这种表达的可能影响。选择 12 例无 RR 治疗的 MS 患者,采集外周血单核细胞。通过 qrt-PCR 检测单核细胞中 P2X7R、IL-1β 和 CD39 的表达。评估 GA 对 BzATP(一种有效的 P2X7R 激动剂)刺激的单核细胞表达的体外影响。同样对 10 名健康供体(HD)进行了研究。最后,5 例 MS 患者接受 GA 治疗,同样在治疗前、治疗后 3 个月和 12 个月采集单核细胞进行研究。患者与对照组之间 P2X7R、IL-1β 和 CD39 的表达无差异。在 MS Bz-ATP 刺激的单核细胞中,GA 预处理明显下调 P2X7R(p=0.003),但 IL-1β 的表达也呈下降趋势(p=0.07)。相反,CD39 呈上升趋势(p=0.07)。在 HD 中也发现了类似的证据。GA 体内治疗诱导的表达减少在 P2X7R 和 CD39 中很明显(p<0.05),但在治疗 12 个月后,IL-1β 仅无显著差异。来自 MS 和对照组的单核细胞均表达 P2X7R、IL-1β 和 CD39,GA 似乎干扰了这种表达。

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