Rifampicin inhibits microglial inflammation and improves neuron survival against inflammation
Rifampicin inhibits microglial inflammation and improves neuron survival against inflammation
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DOI：
10.1016/j.brainres.2011.04.019
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发表时间：
2011-06-13
期刊：
影响因子：
2.9
通讯作者：
Tao, Enxiang
中科院分区：
文献类型：
--
作者：
Bi, Wei;Zhu, Lihong;Tao, Enxiang
小胶质细胞激活在神经退行性疾病的病理生理学中发挥着重要作用，抑制小胶质细胞激活可以阻止神经退行性疾病的进展。利福平是一种杀菌抗生素，可引起免疫抑制。我们推测利福平可能通过抑制促炎介质的产生，从而抑制小胶质细胞的活化，从而起到神经保护作用。在本研究中，我们研究了利福平对BV 2小胶质细胞内脂多糖（LPS）诱导的促炎介质及其信号通路的影响。我们还使用小胶质细胞和神经元的共培养物评估了利福平的神经保护作用。我们的研究结果表明，利福平抑制LPS刺激诱导型一氧化氮合酶，环氧合酶-2，肿瘤坏死因子-α，白细胞介素-1 β的表达，以及一氧化氮和前列腺素E-2的生产。此外，利福平通过阻断核转录因子NF-κ B抑制剂的降解来抑制LPS诱导的核因子-κ B活化。利福平抑制有丝分裂原活化蛋白激酶的磷酸化，但不抑制蛋白激酶B。在小胶质细胞-神经元共培养系统中，用利福平预孵育小胶质细胞可降低神经毒性并提高神经元存活率。总之，这些发现表明，利福平，其抗炎特性，可能是一种新的治疗神经退行性疾病。(C)2011 Elsevier B. V.保留所有权利。
Microglial activation plays an important role in the pathophysiology of neurodegenerative diseases, and suppression of microglial activation prevents the progression of neurodegeneration. Rifampicin, a bacteriocidal antibiotic, induces immunosuppression. We hypothesized that rifampicin might be neuroprotective by inhibiting the production of pro-inflammatory mediators, thereby suppressing microglial activation. In the present study, we examined the effects of rifampicin on the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators and their signaling pathways in BV2 microglia. We also assessed the neuroprotective effects of rifampicin using a co-culture of microglia and neurons. Our results showed that rifampicin inhibited the LPS-stimulated expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alpha, and interleukin-1 beta, as well as the production of nitric oxide and prostaglandin E-2. Moreover, rifampicin suppressed LPS-induced nuclear factor-kappa B activation by blocking the degradation of the inhibitor of the nuclear transcription factor NF-kappa B. Rifampicin inhibited the phosphorylation of mitogen activated protein kinases, although protein kinase B was not inhibited. Preincubation of microglia with rifampicin reduced neurotoxicity and improved neuron survival in a microglia-neuronal co-culture system. Taken together, these findings suggest that rifampicin, with its anti-inflammatory properties, might be a novel treatment for neurodegenerative diseases. (C) 2011 Elsevier B.V. All rights reserved.