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首页> 外文期刊>Journal of neuroinflammation >The CCL2 synthesis inhibitor bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis
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The CCL2 synthesis inhibitor bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis

机译：CCL2合成抑制剂结合蛋白靶向神经血管单位的细胞，并抑制实验性自身免疫性脑脊髓炎

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Background Production of the chemokine CCL2 by cells of the neurovascular unit (NVU) drives critical aspects of neuroinflammation. Suppression of CCL2 therefore holds promise in treating neuroinflammatory disease. Accordingly, we sought to determine if the compound bindarit, which inhibits CCL2 synthesis, could repress the three NVU sources of CCL2 most commonly reported in neuroinflammation 鈥?astrocytes, microglia and brain microvascular endothelial cells (BMEC) 鈥?as well as modify the clinical course of neuroinflammatory disease. Methods The effect of bindarit on CCL2 expression by cultured murine astrocytes, microglia and BMEC was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bindarit action on mouse brain and spinal cord in vivo was similarly investigated by qRT-PCR following LPS injection in mice. And to further gauge the potential remedial effects of bindarit on neuroinflammatory disease, its impact on the clinical course of experimental autoimmune encephalomyelitis (EAE) in mice was also explored. Results Bindarit repressed CCL2 expression by all three cultured cells, and antagonized upregulated expression of CCL2 in both brain and spinal cord in vivo following LPS administration. Bindarit also significantly modified the course and severity of clinical EAE, diminished the incidence and onset of disease, and evidenced signs of disease reversal. Conclusion Bindarit was effective in suppressing CCL2 expression by cultured NVU cells as well as brain and spinal cord tissue in vivo. It further modulated the course of clinical EAE in both preventative and therapeutic ways. Collectively, these results suggest that bindarit might prove an effective treatment for neuroinflammatory disease.
机译：背景神经血管单位（NVU）的细胞产生趋化因子CCL2驱动了神经炎症的关键方面。因此，抑制CCL2在治疗神经炎性疾病方面有希望。因此，我们试图确定抑制CCL2合成的化合物bindarit是否能抑制神经炎症中最常报道的三种NCLU CCL2来源“星形胶质细胞，小胶质细胞和脑微血管内皮细胞（BMEC）”，以及如何改变临床神经炎性疾病的病程。方法采用定量逆转录聚合酶链反应（qRT-PCR）方法检测结合蛋白对培养的鼠星形胶质细胞，小胶质细胞和BMEC CCL2表达的影响。在小鼠中注射LPS后，通过qRT-PCR类似地研究了Bindarit在体内对小鼠脑和脊髓的作用。为了进一步评估必达利对神经炎性疾病的潜在治疗作用，还探讨了其对小鼠实验性自身免疫性脑脊髓炎（EAE）临床过程的影响。结果在使用LPS后，Bindarit抑制了所有三种培养细胞的CCL2表达，并拮抗了CCL2在脑和脊髓中的表达。 Bindarit还显着改变了临床EAE的病程和严重程度，减少了疾病的发生率和发作，并显示出疾病逆转的迹象。结论Bindarit能有效抑制培养的NVU细胞以及脑和脊髓组织的CCL2表达。它以预防和治疗方式进一步调节了临床EAE的进程。总体而言，这些结果表明，必得利可能证明是治疗神经炎性疾病的有效方法。

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