Differential mRNA expression of neuroinflammatory modulators in the spinal cord and thalamus of type 2 diabetic monkeys
在2型糖尿病猴的脊髓与丘脑中神经炎症调节因子mRNA表达的差异性
Huiping Ding
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
These authors contributed equally to this work.Search for more papers by this authorCorresponding Author
Norikazu Kiguchi
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Department of Pharmacology, Wakayama Medical University, Wakayama, Japan
These authors contributed equally to this work.Correspondence
Norikazu Kiguchi, Department of Pharmacology, Wakayama Medical University, Wakayama city, Wakayama 641-0012, Japan.
Tel: +81 73 441 0629
Fax: +81 73 446 3806
Email: [email protected]
Search for more papers by this authorShiroh Kishioka
Department of Pharmacology, Wakayama Medical University, Wakayama, Japan
Search for more papers by this authorTao Ma
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Department of Internal Medicine – Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorChristopher M. Peters
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorMei-Chuan Ko
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorHuiping Ding
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
These authors contributed equally to this work.Search for more papers by this authorCorresponding Author
Norikazu Kiguchi
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Department of Pharmacology, Wakayama Medical University, Wakayama, Japan
These authors contributed equally to this work.Correspondence
Norikazu Kiguchi, Department of Pharmacology, Wakayama Medical University, Wakayama city, Wakayama 641-0012, Japan.
Tel: +81 73 441 0629
Fax: +81 73 446 3806
Email: [email protected]
Search for more papers by this authorShiroh Kishioka
Department of Pharmacology, Wakayama Medical University, Wakayama, Japan
Search for more papers by this authorTao Ma
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Department of Internal Medicine – Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorChristopher M. Peters
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorMei-Chuan Ko
Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorAbstract
enBackground
Given that diabetes-associated complications are closely associated with neuroinflammation, it is imperative to study potential changes in neuroinflammatory modulators in the central nervous system of diabetic primates.
Methods
The mRNA levels of pro- and anti-inflammatory cytokines, toll-like receptors (TLRs), growth factors, and cannabinoid receptors were compared in the spinal dorsal horn (SDH) and thalamus of naturally occurring type 2 diabetic monkeys and an age-matched control group using reverse transcription and quantitative real-time polymerase chain reaction.
Results
In the SDH of diabetic monkeys, mRNA levels of proinflammatory cytokines (i.e. interleukin [IL]-1β and tumor necrosis factor [TNF] α), TLR1, and TLR2 were increased, whereas mRNA levels of IL-10, an anti-inflammatory cytokine, were decreased. No changes were observed in the mRNA levels of growth factors and cannabinoid receptors. In line with the mRNA data, TNFα immunoreactivity was significantly increased in diabetic monkeys. Moreover, mRNA expression levels of IL-1β, TNFα, TLR1, and TLR2 in the SDH were positively correlated with plasma glucose concentrations in all monkeys.
Conclusions
Several ligands and receptors involved in neuroinflammation are simultaneously dysregulated in the spinal cord of diabetic monkeys. This primate disease model will facilitate the design of novel treatment approaches to ameliorate neuroinflammation-driven adverse effects in diabetic patients.
Abstract
zh摘要
背景
由于糖尿病相关的并发症与神经炎症密切相关, 因此我们需要在糖尿病灵长类动物的中枢神经系统中对神经炎症调节因子的潜在变化进行研究。
方法
在自然发生2型糖尿病的猴子以及年龄匹配的对照组猴子的脊髓背角(spinal dorsal horn,SDH)与丘脑中, 使用逆转录与定量实时聚合酶链式反应法, 比较两组之间促炎性与抗炎性细胞因子、Toll样受体(toll like receptors,TLRs)、生长因子以及大麻素受体的mRNA水平是否具有差异。
结果
在糖尿病猴的SDH中, 促炎性细胞因子(亦即白细胞介素[IL]- 1β与肿瘤坏死因子[TNF]α)、TLR1与TLR2的mRNA水平升高, 然而抗炎性细胞因子IL-10的mRNA水平却下降了。没有观察到生长因子与大麻素受体的mRNA水平有变化。在糖尿病猴中还观察到TNFα的免疫反应性显著增加, 这与mRNA的数据一致。此外, 在所有猴子的SDH中IL-1β、TNFα、TLR1以及TLR2的mRNA表达水平都与血糖浓度呈正相关。
结论
在糖尿病猴的脊髓中多种参与神经炎症的配体与受体都同时失调了。使用这种灵长类动物疾病模型有助于我们设计新的治疗方法来改善糖尿病患者合并的神经炎症导致的不良作用。
Supporting Information
| Filename | Description |
|---|---|
| jdb12780-sup-0001-AppendixS1.pdfPDF document, 251.9 KB |
Figure S1. Correlation between plasma glucose levels and the expression of pro-inflammatory cytokines in the spinal dorsal horn of monkeys. Figure S2. Correlation between plasma glucose levels and the expression of anti-inflammatory cytokines in the spinal dorsal horn of monkeys. Figure S3. Correlation between plasma glucose levels and the expression of interleukin-10 in the thalamus of monkeys. Figure S4. Correlation between plasma glucose levels and the expression of toll-like receptors in the spinal dorsal horn of monkeys. |
| jdb12780-sup-0002-TableS1.pdfPDF document, 49.2 KB | Table S1. General characteristics of non-diabetic and type 2 diabetic monkeys. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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