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Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages
Inflammation ( IF 4.5 ) Pub Date : 2021-08-21 , DOI: 10.1007/s10753-021-01507-x
Shangrila Parvin 1 , Clintoria R Williams 1, 2 , Simone A Jarrett 1 , Sandra M Garraway 1, 1
Affiliation  

Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.



中文翻译:


脊髓损伤会增加急性和亚慢性阶段肾脏中促炎细胞因子的表达



越来越多的证据支持脊髓损伤(SCI)会产生强大的炎症可塑性。我们之前表明 SCI 后脊髓中促炎细胞因子肿瘤坏死因子 (TNF)α 增加。 SCI 还会诱发全身炎症反应,影响周围器官功能。肾脏在维持心血管健康方面发挥着重要作用。然而,SCI 引起的肾脏炎症反应以及随后对肾功能的影响尚未得到很好的表征。本研究调查了高位和低位胸部 (T) SCI 在急性和亚慢性时间点对肾脏中 C-fos、TNFα、白细胞介素 (IL)-1β 和 IL-6 表达的影响。成年 C57BL/6 小鼠在 T4 或 T10 接受中度挫伤 SCI 或假手术。未受伤的小鼠作为幼稚对照。损伤后 1 天和 14 天,评估肾脏和脊髓中促炎细胞因子 IL-1β、IL-6、TNFα 和 C-fos 的 mRNA 水平以及 TNFα 和 C-fos 蛋白表达。两次损伤后 1 天,肾脏和脊髓中所有目标的 mRNA 水平均大幅增加。 SCI 后第 14 天,脊髓中的 IL-6 和 TNFα 仍然升高,而肾脏中的 C-fos、IL-6 和 TNFα 水平仅在第 10 次 SCI 后才维持在肾脏中。 T4 和 T10 SCI 后 1 天,肾脏中 TNFα 蛋白显着上调。总体而言,这些结果清楚地表明 SCI 会诱发严重的全身炎症,并延伸至肾脏。因此,肾脏炎症的存在可显着影响 SCI 后肾脏的病理生理学和功能。

更新日期:2021-08-23
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