Transmissible Gastroenteritis Virus Infection Up-Regulates FcRn Expression via Nucleocapsid Protein and Secretion of TGF-β in Porcine Intestinal Epithelial Cells
Transmissible Gastroenteritis Virus Infection Up-Regulates FcRn Expression via Nucleocapsid Protein and Secretion of TGF-β in Porcine Intestinal Epithelial Cells
复制标题
传染性胃肠炎病毒感染通过核衣壳蛋白上调 FcRn 表达和猪肠上皮细胞中 TGF-β 的分泌。
DOI：
10.3389/fmicb.2019.03085
复制
发表时间：
2020-01-21
影响因子：
5.2
通讯作者：
Li, Zili
中科院分区：
文献类型：
--
作者：
Qian, Shaoju;Gao, Zitong;Li, Zili
传染性胃肠炎病毒（TGEV）是一种猪肠道冠状病毒，可导致仔猪致命的严重水样腹泻。新生儿Fc受体（FcRn）是唯一的IgG转运受体，其在病毒刺激下在粘膜表面表达，显着增强粘膜免疫。我们利用TGEV作为模型病原体来探讨FcRn在整体肠粘膜免疫中抵抗病毒入侵的作用。 TGEV 通过激活猪小肠上皮 (IPEC-J2) 细胞中的 NF-kappa B 信号传导诱导 FcRn 表达，但其潜在机制尚不清楚。首先，使用小干扰RNA，我们发现TGEV通过TLR3、TLR9和RIG-I上调FcRn表达。此外，TGEV 诱导 IL-1β、IL-6、IL-8、TGF-β 和 TNF-α 产生。 TGF-β 刺激的 IPEC-J2 细胞高度上调 FcRn 表达，而用 JNK 特异性抑制剂处理则下调表达。 TGEV 核衣壳 (N) 蛋白还通过 NF-kappa B 信号通路增强 FcRn 启动子活性，其中心区域 (aa 128-252) 对于 FcRn 激活至关重要。此外，N 蛋白介导的 FcRn 上调可促进 IgG 转胞吞作用。由此可见，TGEV N蛋白和TGF-β上调FcRn表达，进一步阐明TGEV上调FcRn表达的分子机制。
Transmissible gastroenteritis virus (TGEV) is a porcine intestinal coronavirus that causes fatal severe watery diarrhea in piglets. The neonatal Fc receptor (FcRn) is the only IgG transport receptor, its expression on mucosal surfaces is triggered upon viral stimulation, which significantly enhances mucosal immunity. We utilized TGEV as a model pathogen to explore the role of FcRn in resisting viral invasion in overall intestinal mucosal immunity. TGEV induced FcRn expression by activating NF-kappa B signaling in porcine small intestinal epithelial (IPEC-J2) cells, however, the underlying mechanisms are unclear. First, using small interfering RNAs, we found that TGEV up-regulated FcRn expression via TLR3, TLR9 and RIG-I. Moreover, TGEV induced IL-1 beta, IL-6, IL-8, TGF-beta, and TNF-alpha production. TGF-beta-stimulated IPEC-J2 cells highly up-regulated FcRn expression, while treatment with a JNK-specific inhibitor down-regulated the expression. TGEV nucleocapsid (N) protein also enhanced FcRn promoter activity via the NF-kappa B signaling pathway and its central region (aa 128-252) was essential for FcRn activation. Additionally, N protein-mediated FcRn up-regulation promotes IgG transcytosis. Thus, TGEV N protein and TGF-beta up-regulated FcRn expression, further clarifying the molecular mechanism of up-regulation of FcRn expression by TGEV.