文献类型：期刊文献

英文题名：IL-8 Links NF-κB and Wnt/β-Catenin Pathways in Persistent Inflammatory Response Induced by Chronic Helicobacter pylori Infection

作者：Lin, L.[1];Xie, B.[2];Shi, J.[3];Zhou, C. M.[4];Yi, J.[2];Chen, J.[2];He, J. X.[5];Wei, H. L.[2]

第一作者：Lin, L.

通信作者：Lin, L[1]

机构：[1]Gansu Prov Matern & Child Care Hosp, Dept Hematol & Oncol, Lanzhou 730050, Gansu, Peoples R China;[2]Lanzhou Univ, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, Lanzhou 730000, Gansu, Peoples R China;[3]Lanzhou Univ, Hosp 2, Dept Blood Transfus, Lanzhou 730000, Gansu, Peoples R China;[4]Lanzhou Univ, Hosp 1, Dept Clin Lab Ctr, Lanzhou 730000, Gansu, Peoples R China;[5]Gansu Univ Chinese Med, Basic Med Coll, Lanzhou 730000, Gansu, Peoples R China

第一机构：Gansu Prov Matern & Child Care Hosp, Dept Hematol & Oncol, Lanzhou 730050, Gansu, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Matern & Child Care Hosp, Dept Hematol & Oncol, Lanzhou 730050, Gansu, Peoples R China.

年份：2023

卷号：57

期号：4

起止页码：735

外文期刊名：MOLECULAR BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001014967600006)】；

基金：This work was funded by National Natural Science Foundation of China (no. 81503377), Natural Science Fund Project of Gansu Province (no. 22JR5RA729) and the Higher Education Innovation Fund Project of Gansu Province (no. 2021B-021). The funders have no role in the study.

语种：英文

外文关键词：Helicobacter pylori; interleukin 8; Wnt2; NF-kappa B; signaling pathway; inflammation; gastric cancer

摘要：Helicobacter pylori (H. pylori) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic H. pylori infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-kappa B p65, IL-8, Wnt2 and beta-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of H. pylori in mice was evaluated by rapid urease test, H&E staining and Warthin-Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in H. pylori infected gastric mucosal cells along with activation of NF-kappa B signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of Wnt2. Studies in chronic H. pylori infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-kappa B signaling pathway and Wnt2 expression, we found that H. pylori infection activated NF-kappa B signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/beta-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively, H. pylori chronic infection may continuously lead to persistent inflammatory response: activate NF-kappa B path-way, promote IL-8 release and thereby activate Wnt/beta-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.