鸟氨酸脱羧酶
幽门螺杆菌
生物
炎症
免疫系统
胃炎
免疫学
肠化生
胃粘膜
慢性胃炎
癌症研究
基因敲除
胃
细胞凋亡
酶
生物化学
遗传学
作者
Yvonne L. Latour,Johanna C. Sierra,Kara M. McNamara,Thaddeus M. Smith,Paula B. Luis,Claus M. Schneider,Alberto G. Delgado,Daniel P. Barry,Margaret M. Allaman,M. Wade Calcutt,Kevin L. Schey,M. Blanca Piazuelo,Alain P. Gobert,Keith T. Wilson
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2022-07-27
卷期号:209 (4): 796-805
被引量:1
标识
DOI:10.4049/jimmunol.2100795
摘要
Abstract Colonization by Helicobacter pylori is associated with gastric diseases, ranging from superficial gastritis to more severe pathologies, including intestinal metaplasia and adenocarcinoma. The interplay of the host response and the pathogen affect the outcome of disease. One major component of the mucosal response to H. pylori is the activation of a strong but inefficient immune response that fails to control the infection and frequently causes tissue damage. We have shown that polyamines can regulate H. pylori–induced inflammation. Chemical inhibition of ornithine decarboxylase (ODC), which generates the polyamine putrescine from l-ornithine, reduces gastritis in mice and adenocarcinoma incidence in gerbils infected with H. pylori. However, we have also demonstrated that Odc deletion in myeloid cells enhances M1 macrophage activation and gastritis. Here we used a genetic approach to assess the specific role of gastric epithelial ODC during H. pylori infection. Specific deletion of the gene encoding for ODC in gastric epithelial cells reduces gastritis, attenuates epithelial proliferation, alters the metabolome, and downregulates the expression of immune mediators induced by H. pylori. Inhibition of ODC activity or ODC knockdown in human gastric epithelial cells dampens H. pylori–induced NF-κB activation, CXCL8 mRNA expression, and IL-8 production. Chronic inflammation is a major risk factor for the progression to more severe pathologies associated with H. pylori infection, and we now show that epithelial ODC plays an important role in mediating this inflammatory response.
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