Qian Shaoju, Li Chenxi, Liu Xi, Jia Xiangchao, Xiao Yuncai, Li Zili
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China.
Microorganisms. 2021 Apr 20;9(4):879. doi: 10.3390/microorganisms9040879.
The neonatal Fc receptor (FcRn) transports maternal immunoglobulin G (IgG) to the foetus or newborn and protects the IgG from degradation. FcRn is expressed in several porcine tissues and cell types and its expression levels are regulated by immune and inflammatory events. IPEC-J2 cells are porcine intestinal columnar epithelial cells that were isolated from neonatal piglet mid-jejunum. We hypothesized that transforming growth factor β1 (TGF-β1) upregulated pFcRn expression in IPEC-J2 cells. To test this hypothesis, we treated IPEC-J2 cells with TGF-β1 and demonstrated that porcine FcRn (pFcRn) expression was significantly increased. SP600125, a specific mitogen-activated protein kinase (MAPK) inhibitor, reduced TGF-β1-induced pFcRn expression in IPEC-J2 cells. We performed luciferase reporter assays and showed that the c-JUN sensitive region of the pFcRn promoter gene was located between positions -1215 and -140. The c-JUN sequence, in combination with the pFcRn promoter, regulated luciferase reporter activity in response to TGF-β1 stimulation. Chromatin immunoprecipitation confirmed that there were three c-JUN binding sites in the pFcRn promoter. Furthermore, in addition to increased pFcRn expression, TGF-β1 also enhanced IgG transcytosis in IPEC-J2 cells. In summary, our data showed that the modulation of JNK/MAPK signaling by TGF-β1 was sufficient to upregulate pFcRn expression.
新生儿Fc受体（FcRn）将母体免疫球蛋白G（IgG）转运至胎儿或新生儿体内，并保护IgG不被降解。FcRn在多种猪组织和细胞类型中表达，其表达水平受免疫和炎症事件调控。IPEC-J2细胞是从新生仔猪空肠中段分离得到的猪肠柱状上皮细胞。我们假设转化生长因子β1（TGF-β1）上调IPEC-J2细胞中pFcRn的表达。为验证这一假设，我们用TGF-β1处理IPEC-J2细胞，结果显示猪FcRn（pFcRn）的表达显著增加。SP600125是一种特异性丝裂原活化蛋白激酶（MAPK）抑制剂，它可降低TGF-β1诱导的IPEC-J2细胞中pFcRn的表达。我们进行了荧光素酶报告基因检测，结果表明pFcRn启动子基因的c-JUN敏感区位于-1215至-140位之间。c-JUN序列与pFcRn启动子共同作用，可调节荧光素酶报告基因活性以响应TGF-β1刺激。染色质免疫沉淀证实pFcRn启动子中有三个c-JUN结合位点。此外，除了增加pFcRn的表达外，TGF-β1还增强了IPEC-J2细胞中IgG的转胞吞作用。总之，我们的数据表明TGF-β1对JNK/MAPK信号通路的调节足以上调pFcRn的表达。
