Dose-dependent anti-inflammatory and neuroprotective effects of an ανβ3 integrin-binding peptide.

Dose-dependent anti-inflammatory and neuroprotective effects of an ανβ3 integrin-binding peptide.
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DOI:
10.1155/2013/268486
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发表时间:
2013
影响因子:
4.6
通讯作者:
Fang M
Fang M
中科院分区:
医学3区
文献类型:
--
作者:
Han S;Zhang F;Hu Z;Sun Y;Yang J;Davies H;Yew DT;Fang M

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以往的研究表明,通过靶向参与跨内皮迁移的整合素来预防白细胞浸润可能会抑制神经炎性疾病的临床和病理特征。本研究旨在研究α ν β3整合素结合肽C16在急性实验性变态反应性脑脊髓炎(EAE)大鼠模型中的作用。采用多种组织学和免疫组织化学染色、电镜观察、ELISA测定、Western blot和磁共振成像(MRI)来评估不同治疗的EAE模型的脑和脊髓中的炎症、轴突损失、神经元凋亡、白色物质脱髓鞘和胶质增生的程度。结果表明,C16处理可抑制白细胞和巨噬细胞的大量聚集和浸润,降低细胞因子肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)的表达水平。C16给药组在疾病高峰时间的临床评分也显著较低。此外,星形胶质细胞增生、脱髓鞘、神经元死亡和轴突丢失在C16治疗的EAE动物中均减轻,这可能归因于微环境的改善。这些数据表明,C16肽可以作为一种保护剂,通过减弱炎症进展,从而影响神经炎症疾病过程中的一些促炎细胞因子的表达。
Previous studies have shown that prevention of leukocyte infiltration by targeting integrins involved in transendothelial migration may suppress the clinical and pathological features of neuroinflammatory disease. This study was designed to investigate the effects of C16, an α ν β3 integrin-binding peptide, in an acute experimental allergic encephalomyelitis (EAE) rat model. Multiple histological and immunohistochemical staining, electron microscopy observation, ELISA assay, Western blot, and magnetic resonance imaging (MRI) were employed to assess the degree of inflammation, axonal loss, neuronal apoptosis, white matter demyelination, and extent of gliosis in the brain and spinal cord of differently treated EAE models. The results showed that C16 treatment could inhibit extensive leukocyte and macrophage accumulation and infiltration and reduce cytokine tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) expression levels. A significantly lower clinical score at the peak time of disease was also demonstrated in the C16 treated group. Moreover, astrogliosis, demyelination, neuronal death, and axonal loss were all alleviated in C16 treated EAE animals, which may be attributed to the improvement of microenvironment. The data suggests that C16 peptide may act as a protective agent by attenuating inflammatory progression and thus affecting the expression of some proinflammatory cytokines during neuroinflammatory disease.
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