Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Department of Pharmacology, Emory University, Atlanta, Georgia, United States of America.
PLoS One. 2021 Jul 19;16(7):e0254632. doi: 10.1371/journal.pone.0254632. eCollection 2021.
Superoxide radicals and other reactive oxygen species (ROS) are implicated in influenza A virus-induced inflammation. In this in vitro study, we evaluated the effects of TG6-44, a novel quinazolin-derived myeloperoxidase-specific ROS inhibitor, on influenza A virus (A/X31) infection using THP-1 lung monocytic cells and freshly isolated peripheral blood mononuclear cells (PBMC). TG6-44 significantly decreased A/X31-induced ROS and virus-induced inflammatory mediators in THP-1 cells (IL-6, IFN-γ, MCP-1, TNF-α, MIP-1β) and in human PBMC (IL-6, IL-8, TNF-α, MCP-1). Interestingly, TG6-44-treated THP-1 cells showed a decrease in percent cells expressing viral nucleoprotein, as well as a delay in translocation of viral nucleoprotein into the nucleus. Furthermore, in influenza A virus-infected cells, TG6-44 treatment led to suppression of virus-induced cell death as evidenced by decreased caspase-3 activation, decreased proportion of Annexin V+PI+ cells, and increased Bcl-2 phosphorylation. Taken together, our results demonstrate the anti-inflammatory and anti-infective effects of TG6-44.
超氧自由基和其他活性氧物种（ROS）与甲型流感病毒诱导的炎症有关。在这项体外研究中，我们使用 THP-1 肺单核细胞和新鲜分离的外周血单核细胞（PBMC）评估了新型喹唑啉衍生的髓过氧化物酶特异性 ROS 抑制剂 TG6-44 对甲型流感病毒（A/X31）感染的影响。TG6-44 可显著降低 A/X31 诱导的 THP-1 细胞中的 ROS 和病毒诱导的炎症介质（IL-6、IFN-γ、MCP-1、TNF-α、MIP-1β）和人 PBMC（IL-6、IL-8、TNF-α、MCP-1）。有趣的是，用 TG6-44 处理的 THP-1 细胞中表达病毒核蛋白的细胞百分比下降，病毒核蛋白向细胞核内易位的时间延迟。此外，在感染甲型流感病毒的细胞中，TG6-44 处理可抑制病毒诱导的细胞死亡，这表现为 caspase-3 激活减少、 Annexin V+PI+细胞比例降低和 Bcl-2 磷酸化增加。总之，我们的结果表明 TG6-44 具有抗炎和抗感染作用。
