Rifampicin improves neuronal apoptosis in LPS-stimulated co‑cultured BV2 cells through inhibition of the TLR-4 pathway.

Rifampicin improves neuronal apoptosis in LPS-stimulated co‑cultured BV2 cells through inhibition of the TLR-4 pathway.
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利福平通过抑制 TLR-4 途径改善 LPS 刺激的共培养 BV2 细胞中的神经元凋亡

DOI:
10.3892/mmr.2014.2480
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发表时间:
2014-10
影响因子:
3.4
通讯作者:
Tao E
Tao E
中科院分区:
医学4区
文献类型:
--
作者:
Bi W;Zhu L;Jing X;Zeng Z;Liang Y;Xu A;Liu J;Xiao S;Yang L;Shi Q;Guo L;Tao E

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抑制小胶质细胞活化的药物作为神经退行性疾病中的神经保护的候选药物引起了人们的注意。近年来,利福平引起的免疫抑制作用成为研究者关注的焦点。我们先前的研究表明,利福平抑制脂多糖(LPS)诱导的促炎介质的产生,并改善炎症中的神经元存活;然而,利福平抑制小胶质细胞炎症及其神经保护作用的机制尚未完全了解。在这项研究中,我们研究了利福平对LPS诱导的小鼠小胶质细胞BV 2细胞形态学变化的影响。在此基础上,我们研究了利福平对LPS刺激的BV 2小胶质细胞Toll样受体4(TLR-4)和核因子-κB(NF-κB)信号通路的影响。此外,我们将BV 2小胶质细胞与神经元共培养,观察利福平的间接神经保护作用。利福平抑制LPS刺激的TLR-4基因的表达。当神经元与LPS刺激的BV 2小胶质细胞共培养时,用利福平预处理增加了神经元活力并减少了凋亡细胞的数量。总之,这些发现表明,利福平,其抗炎特性,可能是一个有前途的代理用于治疗神经退行性疾病。
Agents inhibiting microglial activation are attracting attention as candidate drugs for neuroprotection in neurodegenerative diseases. Recently, researchers have focused on the immunosuppression induced by rifampicin. Our previous study showed that rifampicin inhibits the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators and improves neuron survival in inflammation; however, the mechanism through which rifampicin inhibits microglial inflammation and its neuroprotective effects are not completely understood. In this study, we examined the effects of rifampicin on morphological changes induced by LPS in murine microglial BV2 cells. Then we investigated, in BV2 microglia, the effects of rifampicin on two signaling pathway componentss stimulated by LPS, the Toll-like receptor-4 (TLR-4) and the nuclear factor-κB (NF-κB). In addition, we co-cultured BV2 microglia and neurons to observe the indirect neuroprotective effects of rifampicin. Rifampicin inhibited LPS-stimulated expression of the TLR-4 gene. When neurons were co-cultured with LPS-stimulated BV2 microglia, pre-treatment with rifampicin increased neuronal viability and reduced the number of apoptotic cells. Taken together, these findings suggest that rifampicin, with its anti-inflammatory properties, may be a promising agent for the treatment of neurodegenerative diseases.
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