| Autor: |
Rui Xie, Nan You, Wan-Yan Chen, Peng Zhu, Pan Wang, Yi-Pin Lv, Geng-Yu Yue, Xiao-Lin Xu, Jiang-Bo Wu, Jing-Yu Xu, Si-Xu Liu, Mu-Han Lü, Sheng-Qian Yang, Ping Cheng, Fang-Yuan Mao, Yong-Sheng Teng, Liu-Sheng Peng, Jin-Yu Zhang, Ya-Ling Liao, Shi-Ming Yang, Yong-Liang Zhao, Weisan Chen, Quan-Ming Zou, Yuan Zhuang |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Research, Vol 7 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2639-5274 |
| DOI: |
10.34133/research.0409 |
| Popis: |
Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a−/−, Angptl4−/−, and Il17a−/−Angptl4−/− mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K–AKT–NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5–CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K–AKT–NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
