Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Neurochem Int. 2013 Nov;63(5):363-7. doi: 10.1016/j.neuint.2013.07.012. Epub 2013 Aug 6.
Chemokines, a subclass of cytokine superfamily have both pro-inflammatory and migratory role and serve as chemoattractant of immune cells during the inflammatory responses ensuing spinal cord injury (SCI). The chemokines, especially CXCL-1, CXCL-9, CXCL-10 and CXCL-12 contribute significant part in the inflammatory secondary damage of SCI. Inhibiting chemokine's activity and thereby the secondary damage cascades has been suggested as a chemokine-targeted therapeutic approach to SCI. To optimize the inhibition of secondary injury through targeted chemokine therapy, accurate knowledge about the temporal profile of these cytokines following SCI is required. Hence, the present study was planned to determine the serum levels of CXCL-1, CXCL-9, CXCL-10 and CXCL-12 at 3-6h, 7 and 28days and 3m after SCI in male and female SCI patients (n=78) and compare with age- and sex-matched patients with non-spinal cord injuries (NSCI, n=70) and healthy volunteers (n=100). ANOVA with Tukey post hoc analysis was used to determine the differences between the groups. The data from the present study show that the serum level of CXCL-1, CXCL-9 and CXCL-10 peaked on day 7 post-SCI and then declined to the control level. In contrast, significantly elevated level of CXCL-12 persisted for 28 days post SCI. In addition, post-SCI expression of CXCL-12 was found to be sex-dependent. Male SCI patients expressed significantly higher CXCL-12 when compared to control and SCI female. We did not observe any change in chemokines level of NSCI. Further, the age of the patients did not influence chemokines expression after SCI. These observations along with SCI-induced CSF-chemokine level should contribute to the identification of selective and temporal chemokine targeted therapy after SCI.
趋化因子是细胞因子超家族的一个子类,具有促炎和趋化作用,在脊髓损伤 (SCI) 后炎症反应中作为免疫细胞的趋化因子。趋化因子,特别是 CXCL-1、CXCL-9、CXCL-10 和 CXCL-12,在 SCI 的炎症继发性损伤中起着重要作用。抑制趋化因子的活性,从而抑制继发性损伤级联反应,已被认为是一种针对 SCI 的趋化因子靶向治疗方法。为了通过靶向趋化因子治疗优化继发性损伤的抑制,需要准确了解这些细胞因子在 SCI 后的时间分布。因此,本研究旨在确定雄性和雌性 SCI 患者 (n=78) 在 SCI 后 3-6h、7 天和 28 天及 3 个月时血清中 CXCL-1、CXCL-9、CXCL-10 和 CXCL-12 的水平,并与年龄和性别匹配的非脊髓损伤患者 (n=70) 和健康志愿者 (n=100) 进行比较。采用 ANOVA 与 Tukey 事后分析比较组间差异。本研究的数据显示,CXCL-1、CXCL-9 和 CXCL-10 的血清水平在 SCI 后第 7 天达到峰值,然后降至对照水平。相比之下,CXCL-12 的水平显著升高并持续 28 天。此外,还发现 SCI 后 CXCL-12 的表达具有性别依赖性。与对照和 SCI 女性相比,雄性 SCI 患者表达的 CXCL-12 显著更高。我们没有观察到非脊髓损伤患者的趋化因子水平发生变化。此外,患者的年龄在 SCI 后也不会影响趋化因子的表达。这些观察结果以及 SCI 诱导的 CSF-趋化因子水平,有助于确定 SCI 后选择性和时间性趋化因子靶向治疗的靶点。