The combination effects of licl and the active leflunomide metabolite, A771726, on viral-induced interleukin 6 production and EV-A71 replication.

The combination effects of licl and the active leflunomide metabolite, A771726, on viral-induced interleukin 6 production and EV-A71 replication.
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DOI:
10.1371/journal.pone.0111331
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Hsu JT
Hsu JT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hung HC;Shih SR;Chang TY;Fang MY;Hsu JT

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肠道病毒71(EV-A71)是一种嗜神经病毒,可引起涉及中枢神经系统的严重并发症。没有有效的抗病毒疗法可用于治疗EV-A71感染,并且药物发现工作很少集中于针对这种疾病。因此,本研究的主要目标是发现具有新适应症的现有药物,可以有效抑制EV-A71复制和炎症细胞因子升高。在本研究中,我们发现,LiCl,一种GSK 3 β抑制剂,有效地抑制EV-A71在感染细胞中的复制、凋亡和炎性细胞因子(白细胞介素6、白细胞介素1β)的产生。此外,LiCl和免疫调节剂显示出在抑制EV-A71复制中彼此强烈协同作用。研究结果强调了抑制EV-A71复制引起的后遗症的潜在新治疗方案。
Enterovirus 71 (EV-A71) is a neurotropic virus that can cause severe complications involving the central nervous system. No effective antiviral therapeutics are available for treating EV-A71 infection and drug discovery efforts are rarely focused to target this disease. Thus, the main goal of this study was to discover existing drugs with novel indications that may effectively inhibit EV-A71 replication and the inflammatory cytokines elevation. In this study, we showed that LiCl, a GSK3β inhibitor, effectively suppressed EV-A71 replication, apoptosis and inflammatory cytokines production (Interleukin 6, Interleukin-1β) in infected cells. Furthermore, LiCl and an immunomodular agent were shown to strongly synergize with each other in suppressing EV-A71 replication. The results highlighted potential new treatment regimens in suppressing sequelae caused by EV-A71 replication.
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