PGRN在幽门螺杆菌诱导胃黏膜上皮细胞分泌IL-8中的作用及机制

Role and Mechanism of PGRN in the Secretion of IL-8 by Gastric Mucosal Epithelial Cells Induced by Helicobacter pylori

摘要: 目的：幽门螺杆菌(H. pylori, HP)感染是胃炎发病率和胃癌死亡率逐年增长的主要原因之一。我们前期研究表明PGRN在胃炎组织中的表达增加，HP感染可促进胃黏膜上皮细胞PGRN的表达。因此，本研究旨在探讨HP感染诱导胃黏膜上皮细胞白细胞介素-8 (IL-8)表达变化中PGRN表达的作用及机制，以阐明PGRN在相关炎症反应中的作用。方法与结果：采用实时荧光定量PCR (qRT-PCR)法和ELISA法检测HP26695感染胃上皮细胞中IL-8的表达水平，该作用是通过NF-κB通路介导的。采用qRT-PCR和western blot (WB)检测慢病毒干扰载体PLKO.1-PGRN shRNA-GFP诱导的IL-8在胃上皮细胞中的表达变化。通过干扰PGRN的表达，HP可以诱导胃黏膜上皮细胞P65的磷酸化水平，进而促进胃黏膜上皮细胞中IL-8 mRNA和蛋白的表达。进一步加入NF-κB通路信号抑制剂BAY11-7082，可干扰PGRN对胃黏膜上皮细胞P65磷酸化的影响，并显著抑制HP感染后IL-8的变化。结论：PGRN通过NF-κB信号通路抑制HP感染诱导的IL-8表达上调，在胃炎的发生发展中起重要的抗炎和保护作用。

Abstract: Objective: Helicobacter pylori (H. pylori, HP) infection is one of the main causes of annual growth in the incidence and mortality of gastritis. Our previous study demonstrated increased expression of PGRN in gastritis tissues, and HP infection could promote the expression of PGRN in gastric mucosal epithelial cells. Therefore, the present study is to investigate the role and mechanism of PGRN expression changes in interleukin-8 (IL-8) expression in gastric mucosa epithelial cells induced by HP infection, with the aim to elucidate the role of PGRN in the associated inflammatory response. Methods and Results: The expression levels of IL-8 in gastric epithelial cells infected with H. pylori 26695 were detected by qRT-PCR and ELISA, and this effect was mediated through the NF-κB pathway. Furthermore, quantitative real-time PCR (qRT-PCR) and western blot (WB) were used to measure the expression changes of IL-8 induced by lentivirus interference vector PLKO.1-PGRN shRNA-GFP in gastric epithelial cells in the control group. The expression of IL-8 mRNA and protein in gastric mucosal epithelial cells induced by HP was significantly increased through interference with PGRN expression, which significantly increased P65 phosphorylation induced by HP in gastric epithelial cells. The further addition of BAY11-7082, a signal inhibitor of the NF-κB pathway, could significantly inhibit the HP infection and interfere with the effect of PGRN on P65 phosphorylation in gastric mucosa epithelial cells. Conclusions: PGRN inhibits the elevated expression of IL-8 induced by HP infection through the NF-κB signaling pathway, and thus plays an important anti-inflammatory and protective role in the occurrence and development of gastritis.