Geng Ping, Zhu Haiyan, Zhou Wei, Su Chang, Chen Mingcang, Huang Chenggang, Xia Chengjie, Huang Hai, Cao Yiou, Shi Xunlong
Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, China.
Department of Chemistry, Fudan University, Shanghai, China.
Front Pharmacol. 2020 Oct 6;11:01298. doi: 10.3389/fphar.2020.01298. eCollection 2020.
The natural compound baicalin (BA) possesses potent antiviral properties against the influenza virus. However, the underlying molecular mechanisms of this antiviral activity and whether macrophages are involved remain unclear. In this study, we, therefore, investigated the effect of BA on macrophages.
We studied macrophage recruitment, functional phenotypes (M1/M2), and the cellular metabolism flow cytometry, qRT-PCR, immunofluorescence, a cell culture transwell system, and GC-MS-based metabolomics both in H1N1 A virus-infected mice and .
BA treatment drastically reduced macrophage recruitment (CD11b, F4/80) by approximately 90% while maintaining the proportion of M1-polarized macrophages in the bronchoalveolar lavage fluid of infected mice. This BA-stimulated macrophage M1 phenotype shift was further verified in ANA-1 and primary peritoneal macrophages by measuring macrophage M1 polarization signals (CD86, iNOS, TNF-α, ratio, and IL-1β cleavage). Meanwhile, we observed an activation of the IFN pathway (upregulation of and ), an inhibition of influenza virus replication (as measured by the gene), and distinct cellular metabolic responses in BA-treated cells.
BA triggered macrophage M1 polarization, IFN activation, and other cellular reactions, which are beneficial for inhibition of H1N1 A virus infection.
天然化合物黄芩苷(BA)对流感病毒具有强大的抗病毒特性。然而,这种抗病毒活性的潜在分子机制以及巨噬细胞是否参与其中仍不清楚。因此,在本研究中,我们调查了BA对巨噬细胞的影响。
我们通过流式细胞术、qRT-PCR、免疫荧光、细胞培养Transwell系统以及基于GC-MS的代谢组学,研究了H1N1 A病毒感染小鼠和[此处原文缺失部分内容]中巨噬细胞的募集、功能表型(M1/M2)和细胞代谢情况。
BA处理使感染小鼠支气管肺泡灌洗液中的巨噬细胞募集(CD11b、F4/80)大幅减少约90%,同时维持M1极化巨噬细胞的比例。通过测量巨噬细胞M1极化信号(CD86、iNOS、TNF-α、[此处原文缺失部分内容]比值和IL-1β裂解),在ANA-1和原代腹膜巨噬细胞中进一步证实了BA刺激的巨噬细胞M1表型转变。同时,我们观察到IFN途径的激活([此处原文缺失部分内容]和[此处原文缺失部分内容]上调)、流感病毒复制的抑制(通过[此处原文缺失部分内容]基因测量)以及BA处理细胞中明显的细胞代谢反应。
BA引发巨噬细胞M1极化、IFN激活和其他细胞反应,这些反应有利于抑制H1N1 A病毒感染。