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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\u2013induced 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\u2013induced NF-\u03baB 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.<\/jats:p>","DOI":"10.4049\/jimmunol.2100795","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T04:36:23Z","timestamp":1672720583000},"page":"796-805","source":"Crossref","is-referenced-by-count":9,"title":["Ornithine Decarboxylase in Gastric Epithelial Cells Promotes the Immunopathogenesis of <i>Helicobacter pylori<\/i> Infection"],"prefix":"10.1093","volume":"209","author":[{"given":"Yvonne L","family":"Latour","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna C","family":"Sierra","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9347-0009","authenticated-orcid":false,"given":"Kara M","family":"McNamara","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Program in Cancer Biology, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thaddeus M","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-1023","authenticated-orcid":false,"given":"Paula B","family":"Luis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4215-967X","authenticated-orcid":false,"given":"Claus","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto G","family":"Delgado","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3972-3914","authenticated-orcid":false,"given":"Daniel P","family":"Barry","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-1365","authenticated-orcid":false,"given":"Margaret M","family":"Allaman","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-4699","authenticated-orcid":false,"given":"M Wade","family":"Calcutt","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin L","family":"Schey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Blanca","family":"Piazuelo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-539X","authenticated-orcid":false,"given":"Alain P","family":"Gobert","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-1830","authenticated-orcid":false,"given":"Keith T","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine , Nashville, TN"},{"name":"Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Program in Cancer Biology, Vanderbilt University School of Medicine , Nashville, TN"},{"name":"Veterans Affairs Tennessee Valley Healthcare System , Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"2025021101010423500_r1","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1056\/NEJMoa001999","article-title":"Helicobacter pylori infection and the development of gastric cancer","volume":"345","author":"Uemura","year":"2001","journal-title":"N. 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Endosc."},{"key":"2025021101010423500_r5","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1001\/jama.2013.311","article-title":"Risk of recurrent Helicobacter pylori infection 1 year after initial eradication therapy in 7 Latin American communities","volume":"309","author":"Morgan","year":"2013","journal-title":"JAMA"},{"key":"2025021101010423500_r6","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/hel.12050","article-title":"Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies","volume":"18","author":"Areia","year":"2013","journal-title":"Helicobacter"},{"key":"2025021101010423500_r7","doi-asserted-by":"crossref","first-page":"14904","DOI":"10.1074\/jbc.R116.731661","article-title":"Functions of polyamines in mammals","volume":"291","author":"Pegg","year":"2016","journal-title":"J. Biol. 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Cell Biol."},{"key":"2025021101010423500_r10","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1210\/en.2007-1420","article-title":"Polyamines are essential in embryo implantation: expression and function of polyamine-related genes in mouse uterus during peri-implantation period","volume":"149","author":"Zhao","year":"2008","journal-title":"Endocrinology"},{"key":"2025021101010423500_r11","first-page":"001","article-title":"Polyamines and gut mucosal homeostasis","volume":"2","author":"Timmons","year":"2012","journal-title":"J Gastrointest Dig Syst"},{"key":"2025021101010423500_r12","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/(SICI)1097-4644(20000601)77:3<345::AID-JCB1>3.0.CO;2-P","article-title":"High levels of intracellular polyamines promote histone acetyltransferase activity resulting in chromatin hyperacetylation","volume":"77","author":"Hobbs","year":"2000","journal-title":"J. Cell. Biochem."},{"key":"2025021101010423500_r13","doi-asserted-by":"crossref","first-page":"E751","DOI":"10.1073\/pnas.1614958114","article-title":"Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications","volume":"114","author":"Hardbower","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021101010423500_r14","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00726-019-02719-0","article-title":"The role of polyamines in the regulation of macrophage polarization and function","volume":"52","author":"Latour","year":"2020","journal-title":"Amino Acids"},{"key":"2025021101010423500_r15","first-page":"2959","article-title":"Polyamine content of AKR leukemic cells in relation to the cell cycle","volume":"33","author":"Heby","year":"1973","journal-title":"Cancer Res."},{"key":"2025021101010423500_r16","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1038\/onc.2014.273","article-title":"Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase","volume":"34","author":"Chaturvedi","year":"2015","journal-title":"Oncogene"},{"key":"2025021101010423500_r17","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1093\/carcin\/20.9.1709","article-title":"APC-dependent changes in expression of genes influencing polyamine metabolism, and consequences for gastrointestinal carcinogenesis, in the Min mouse","volume":"20","author":"Erdman","year":"1999","journal-title":"Carcinogenesis"},{"key":"2025021101010423500_r18","doi-asserted-by":"crossref","first-page":"e0127246","DOI":"10.1371\/journal.pone.0127246","article-title":"A phase I trial of DFMO targeting polyamine addiction in patients with relapsed\/refractory neuroblastoma","volume":"10","author":"Saulnier Sholler","year":"2015","journal-title":"PLoS One"},{"key":"2025021101010423500_r19","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1158\/1940-6207.CAPR-08-0042","article-title":"Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial","volume":"1","author":"Meyskens","year":"2008","journal-title":"Cancer Prev. Res. (Phila.)"},{"key":"2025021101010423500_r20","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.3892\/ijo.2014.2597","article-title":"Pharmacological and dietary agents for colorectal cancer chemoprevention: effects on polyamine metabolism (review)","volume":"45","author":"Linsalata","year":"2014","journal-title":"Int. J. Oncol."},{"key":"2025021101010423500_r21","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1053\/j.gastro.2010.06.060","article-title":"Polyamines impair immunity to Helicobacter pylori by inhibiting L-arginine uptake required for nitric oxide production","volume":"139","author":"Chaturvedi","year":"2010","journal-title":"Gastroenterology"},{"key":"2025021101010423500_r22","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1053\/j.gastro.2009.11.054","article-title":"Conditional deletion of I\u03baB-kinase-\u03b2 accelerates Helicobacter-dependent gastric apoptosis, proliferation, and preneoplasia","volume":"138","author":"Shibata","year":"2010","journal-title":"Gastroenterology"},{"key":"2025021101010423500_r23","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.1172\/JCI83585","article-title":"EGFR regulates macrophage activation and function in bacterial infection","volume":"126","author":"Hardbower","year":"2016","journal-title":"J. Clin. 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