Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Exp Biol Med (Maywood). 2022 Nov;247(21):1917-1922. doi: 10.1177/15353702221121609. Epub 2022 Sep 12.
The human bronchial epithelium plays a crucial role in mediating antiviral immune reactions. When double-stranded RNA (dsRNA) binds to the receptor named Toll-like receptor (TLR) 3, activation of antiviral innate immune reactions is initiated by producing interferon (IFN) type I. Then, type I IFN promotes the transcription of IFN-stimulated genes (ISGs). Proteins encoded by ISGs reveal antiviral effects. The IFN-induced transmembrane protein 1 (IFITM1) is an ISG family member that inhibits viral infection by preventing the entry of viruses with a cell membrane. However, IFITM1 expression in human bronchial epithelium remains largely undetermined. Here, we investigated whether IFITM1 is expressed in cultured BEAS-2B bronchial epithelial cells. Polyinosinic:polycytidylic acid (poly I:C) was used for treatment of BEAS-2B as a TLR3 ligand. IFITM1 expression levels were measured using reverse transcription-quantitative PCR and Western blotting. Using RNA interference, we determined the significance of IFN-β and ISG56 on IFITM1 upregulation. Poly I:C treatment significantly upregulated IFITM1 expression in BEAS-2B cells, and it was concentration- and time-dependent. Knockdown of IFN-β or ISG56 decreased poly I:C-induced IFITM1 expression levels. Recombinant IFN-β also increased expression levels of IFITM1. In BEAS-2B cells, IFITM1 expression is upregulated by poly I:C, at least partly, via the TLR3/IFN-β/ISG56 axis. Thus, IFITM1 may contribute to antiviral innate immunity in bronchial epithelium.
人类支气管上皮在介导抗病毒免疫反应中起着至关重要的作用。当双链 RNA(dsRNA)与名为 Toll 样受体(TLR)3 的受体结合时,通过产生干扰素(IFN)I 型来启动抗病毒先天免疫反应的激活。然后,I 型 IFN 促进 IFN 刺激基因(ISGs)的转录。ISGs 编码的蛋白质显示出抗病毒作用。IFN 诱导的跨膜蛋白 1(IFITM1)是 ISG 家族的一员,通过阻止具有细胞膜的病毒进入来抑制病毒感染。然而,人类支气管上皮中 IFITM1 的表达仍在很大程度上未被确定。在这里,我们研究了 IFITM1 是否在培养的 BEAS-2B 支气管上皮细胞中表达。聚肌苷酸:聚胞苷酸(poly I:C)被用作 TLR3 配体来处理 BEAS-2B。使用逆转录定量 PCR 和 Western blot 来测量 IFITM1 表达水平。通过 RNA 干扰,我们确定了 IFN-β 和 ISG56 在 IFITM1 上调中的意义。poly I:C 处理显著上调了 BEAS-2B 细胞中 IFITM1 的表达,且呈浓度和时间依赖性。IFN-β 或 ISG56 的敲低降低了 poly I:C 诱导的 IFITM1 表达水平。重组 IFN-β 也增加了 IFITM1 的表达水平。在 BEAS-2B 细胞中,IFITM1 的表达通过 TLR3/IFN-β/ISG56 轴至少部分地上调由 poly I:C 诱导。因此,IFITM1 可能有助于支气管上皮的抗病毒先天免疫。