幽门螺杆菌CagL变异体功能研究

The function study of Helicobacter pylori CagL variants

目的：CagL作为幽门螺杆菌Cag- T4SS的一个基本组成部分，其通过RGD模体在胃上皮细胞内与整合素α5β1受体结合参与CagA的转运，本研究旨在探讨幽门螺杆菌CagL变异体的功能。方法：在这项研究中,通过组织学分析、体内外IL-8分泌检测、粘附实验和CagA转运实验被采用，发现一种新型的Ass57和Ass58缺失的CagL变异体，该变异体与野生型CagL的功能差别被研究。结果：野生型CagL幽门螺杆菌携带患者，其胃粘膜炎症细胞浸润程度高于CagL变异体携带者（3.20±0.80，1.63±0.32，=0.03）。野生型CagL幽门螺杆菌携带者，其胃粘膜IL-8水平高于CagL变异体携带者（141.57±29.77 pg/mg和104.96±21.50 pg/mg，〈0.01）。野生型CagL组GES-1细胞IL-8分泌含量高于CagL突变组（1544.87±112.61 pg/ml和1277.36±89.19 pg/ml，〈0.01）。CagL突变组的粘附活性低于CagL野生组[（11.38±1.04）×10^6和（16.70±1.47）×10^6，〈0.01）]，CagA的转运实验也出现了相似的结果。结论：我们发现新的CagL变异体可能是通过改变CagL三维结构的稳定性以减弱幽门螺杆菌的致病性。

Objective： CagL, as an essential component of H. pylori Cag- T4SS, can bind to integrin α5β1 receptor on gastric epithelial cells through RGD motif to involve in CagA injection. This study aimed to explore the function of H. pylori CagL varients. Methods：In this study, histological analysis, IL- 8 secretion assay in vivo and in vitro, the adhesion and CagA translocation assay were applied, and we found a novel CagL variant with Asn57 and Asn58 deletions. The function of this variant was studied. Results： Gastric mucosal inflammatory cell infiltration degree was higher in patients with CagL wild H. pylori than that in patients with CagL variant H. pylori （3.20±0.80, 1.63±0.32, =0.03） . The gastric mucosal IL- 8 level in patients with CagL wild H. pylori was higher than that in patients with CagL variant H. pylori （141.57±29.77 pg/mg, 104.96±21.50 pg/mg, 〈0.01） . IL- 8 level from GES- 1 cells was higher in the CagL wild group than that in the CagL variant group （1544.87±112.61 pg/ml, 1277.36±89.19 pg/ml, 〈0.01） . The adhesion activity was lower in the CagL variant group than that in the CagL wild group [（12.38±1.24） ×10^6 , （16.10±1.57） ×10^6,〈0.01] , and the similar result was also found in CagA translocation assay. Conclusion： Based on these studies, the novel CagL variant H. pylori could weak the pathogenicity of H. pylori by the change of stability on the three- dimensional modeling of CagL.