Abstract:
BACKGROUND & AIMS:Despite inducing an inflammatory response, Helicobacter pylori can persist in the gastric mucosa for decades. H pylori expression of cholesterol-α-glucosyltransferase (encoded by cgt) is required for gastric colonization and T-cell activation. We investigated how cgt affects gastric epithelial cells and the host immune response. METHODS:MKN45 gastric epithelial cells, AGS cells, and human primary gastric epithelial cells (obtained from patients undergoing gastrectomy or sleeve resection or gastric antral organoids) were incubated with interferon gamma (IFNG) or interferon beta (IFNB) and exposed to H pylori, including cagPAI and cgt mutant strains. Some cells were incubated with methyl-β-cyclodextrin (to deplete cholesterol from membranes) or myriocin and zaragozic acid to prevent biosynthesis of sphingolipids and cholesterol and analyzed by immunoblot, immunofluorescence, and reverse transcription quantitative polymerase chain reaction analyses. We compared gene expression patterns among primary human gastric cells, uninfected or infected with H pylori P12 wt or P12Δcgt, using microarray analysis. Mice with disruption of the IFNG receptor 1 (Ifngr1-/- mice) and C57BL6 (control) mice were infected with PMSS1 (wild-type) or PMSS1Δcgt H pylori; gastric tissues were collected and analyzed by reverse transcription quantitative polymerase chain reaction or confocal microscopy. RESULTS:In primary gastric cells and cell lines, infection with H pylori, but not cgt mutants, blocked IFNG-induced signaling via JAK and STAT. Cells infected with H pylori were depleted of cholesterol, which reduced IFNG signaling by disrupting lipid rafts, leading to reduced phosphorylation (activation) of JAK and STAT1. H pylori infection of cells also blocked signaling by IFNB, interleukin 6 (IL6), and IL22 and reduced activation of genes regulated by these signaling pathways, including cytokines that regulate T-cell function (MIG and IP10) and anti-microbial peptides such as human β-defensin 3 (hBD3). We found that this mechanism allows H pylori to persist in proximity to infected cells while inducing inflammation only in the neighboring, non-infected epithelium. Stomach tissues from mice infected with PMSS1 had increased levels of IFNG, but did not express higher levels of interferon-response genes. Expression of the IFNG-response gene IRF1 was substantially higher in PMSS1Δcgt-infected mice than PMSS1-infected mice. Ifngr1-/- mice were colonized by PMSS1 to a greater extent than control mice. CONCLUSIONS:H pylori expression of cgt reduces cholesterol levels in infected gastric epithelial cells and thereby blocks IFNG signaling, allowing the bacteria to escape the host inflammatory response. These findings provide insight into the mechanisms by which H pylori might promote gastric carcinogenesis (persisting despite constant inflammation) and ineffectiveness of T-cell-based vaccines against H pylori.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Morey P,Pfannkuch L,Pang E,Boccellato F,Sigal M,Imai-Matsushima A,Dyer V,Koch M,Mollenkopf HJ,Schlaermann P,Meyer TFdoi
10.1053/j.gastro.2017.12.008subject
Has Abstractpub_date
2018-04-01 00:00:00pages
1391-1404.e9issue
5eissn
0016-5085issn
1528-0012pii
S0016-5085(17)36712-4journal_volume
154pub_type
杂志文章相关文献
GASTROENTEROLOGY文献大全abstract::A rapid immunohistochemical method using 5'-bromo-2'-deoxyuridine (BrdU), a thymidine analog, for labeling proliferating epithelial cells was modified and tested for accuracy against standard tritiated thymidine autoradiography (3H-TdR) in rat esophagus, stomach, duodenum, and colon. Either BrdU or 3H-thymidine or bot...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(91)90610-w
更新日期:1991-01-01 00:00:00
abstract:BACKGROUND & AIMS:In the enteric nervous system, neurotransmitters initiate changes in calcium (Ca(2+) responses) in glia, but it is not clear how this process affects intestinal function. We investigated whether Ca(2+)-mediated responses in enteric glia are required to maintain gastrointestinal function. METHODS:We u...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2013.10.061
更新日期:2014-02-01 00:00:00
abstract::Flow cytometry was used to detect the presence and assess the distribution of aneuploid cell populations in eight proctocolectomy specimens from patients with ulcerative colitis. Mucosal samples were taken according to a systematic protocol for flow cytometry, the surrounding tissue was examined histologically, and th...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(91)90068-v
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND & AIMS:The integrin alpha(4)beta(7) mediates homing of effector/memory lymphocytes to the intestine and the mucosa-associated lymphoid tissue. This study examined the ability of alpha(4)beta(7)(hi) CD4(+) T lymphocytes to home to the stomach and their role in immunization-mediated protection against Helicoba...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2000.8548
更新日期:2000-07-01 00:00:00
abstract::It has recently been shown that repeated large-volume paracentesis associated with intravenous albumin infusion is a rapid, effective, and safe therapy of ascites in cirrhosis. To investigate whether intravenous albumin infusion is necessary in the treatment of cirrhotics with large-volume paracentesis, 105 patients w...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0016-5085(88)90691-9
更新日期:1988-06-01 00:00:00
abstract::Confluent monolayers of epithelial cell lines of intestinal derivation may serve as useful models for studies of intestinal epithelial structure and function. Cells of the T84 line appear to be a useful model for studies of Cl- secretion. We now define the fine structure of this cell line, the structural events that o...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(87)91069-9
更新日期:1987-05-01 00:00:00
abstract::We studied chronic intake of diets deficient in or supplemented with linoleic acid to determine whether it affects gastric acid secretion, release of prostaglandin E2, and stress-induced lesions. For 8-10 wk rats were fed three dietary regimens supplying 3.5% (control group), 0.3%, and 10% of total calories as linolei...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(88)90285-5
更新日期:1988-07-01 00:00:00
abstract:BACKGROUND & AIMS:The enteric nervous system (ENS) coordinates essential intestinal functions through the concerted action of diverse enteric neurons (ENs). However, integrated molecular knowledge of EN subtypes is lacking. To compare human and mouse ENs, we transcriptionally profiled healthy ENS from adult humans and ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2020.09.032
更新日期:2020-09-30 00:00:00
abstract::Serum gastrin and gastric endocrine cell numerical densities were examined in 22 patients with long-standing Zollinger-Ellison syndrome who were receiving either ranitidine, omeprazole, or other antisecretory drugs (SMS 201-995 or pirenzepine with or without ranitidine) for long periods of time. Fifteen patients had i...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(89)91620-x
更新日期:1989-04-01 00:00:00
abstract::Increased type III collagen deposition in all layers of the intestinal tract, including the lamina propria, is a common feature of strictures in Crohn's disease. In the present study, it was found that in comparison with fibroblasts from normal or nonstrictured but inflamed intestinal lamina propria, the fibroblasts i...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(92)90314-o
更新日期:1992-06-01 00:00:00
abstract::A variety of noninvasive molecular approaches to colorectal cancer screening are emerging with potential to improve screening effectiveness and user-friendliness. These approaches are based on the sensitive assay of molecular markers in stool, blood, and urine samples. New methods, especially next generation stool-bas...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2010.01.055
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND & AIMS:The vagus nerve negatively regulates macrophage cytokine production via the release of acetylcholine (ACh) and activation of nicotinic acetylcholine receptors (nAChR). In various models of intestinal inflammation, vagus nerve efferent stimulation ameliorates disease. Given the actively constrained cyt...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2009.04.057
更新日期:2009-09-01 00:00:00
abstract::The clinical, endoscopic, histologic, manometric, and esophageal potential difference characteristics of 20 patients with columnar epithelia lining the lower esophagus (Barrett's esophagus) are presented. Endoscopically, two distinct types were identified: a circumferential-type and an island-type Barrett's esophagus....
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::The purpose of this study was to develop an in vitro model of the proximal colon that would permit investigation of the function of colonic bacteria. Five continuous cultures of fecal bacteria were maintained anaerobically in steady state for at least 21 days in a medium simulating ileostomy effluent. The pH was maint...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(85)90017-4
更新日期:1985-06-01 00:00:00
abstract:BACKGROUND & AIMS:We evaluated etanercept, a human soluble tumor necrosis factor receptor: Fc fusion protein, for the treatment of active Crohn's disease. METHODS:Forty-three patients with moderate to severe Crohn's disease were enrolled in an 8-week placebo-controlled trial. Patients were randomized to subcutaneous e...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1053/gast.2001.28674
更新日期:2001-11-01 00:00:00
abstract:BACKGROUND & AIMS:The study and management of reflux esophagitis require an endoscopic classification system founded on esophageal lesions that can be reproducibly identified. The aim of this study was to investigate interobserver agreement for the identification of endoscopic lesions typical of reflux esophagitis. ME...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.1996.v111.pm8698230
更新日期:1996-07-01 00:00:00
abstract:BACKGROUND & AIMS:The sarcomatoid change in cholangiocarcinoma (CC) contributes to more aggressive intrahepatic spread and widespread metastasis. Therefore, the aim of this study was to identify the molecular mechanisms of CC metastasis during tumor progression and sarcomatoid change. METHODS:Using the subtraction sup...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2009.04.015
更新日期:2009-09-01 00:00:00
abstract::For decades, interactions between the enteric neuromuscular apparatus and the central nervous system have served as the primary focus of pathophysiological research in the functional gastrointestinal disorders. The accumulation of patient reports, as well as clinical observations, has belatedly led to an interest in t...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2016.02.028
更新日期:2016-02-18 00:00:00
abstract::A prospective study of 22 patients with antibiotic-associated pseudomembranous colitis demonstrated that the most distal location of the pseudomembranes was noted from 0 to 25 cm from the anus in 17 patients, from 25 to 60 cm from the anus in 3 patients, and greater than 60 cm from the anus in only 2 patients. These d...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1982-12-01 00:00:00
abstract::Serum group I pepsinogen (PG I) levels, basal acid output, and peak acid output (PAO) have been determined in 120 patients, 54 with duodenal ulcer, 14 with prepyloric ulcer, 12 with gastric ulcer, and 40 without ulcer. The correlation between serum PG I and PAO was statistically significant (r = 0.736, P less than 0.0...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract::A new experimental model, the isolated perfused antrectomized pig stomach with intact vagal innervation, was shown to produce pepsinogen and gastric acid upon electrical stimulation of the vagus nerves and by intravascular administration of carbachol (from a basal value of 111 +/- 24 units of pepsin per minute and 0.0...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(88)90353-8
更新日期:1988-11-01 00:00:00
abstract:BACKGROUND & AIMS:It is unclear whether genomic derangement precedes the histological development of dysplasia in ulcerative colitis (UC)-related neoplastic progression. The primary aim of this study was to determine if chromosomal alterations occur early in the progression pathway of UC-related neoplasia. METHODS:Flu...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(97)70173-2
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND/AIMS:Cytokines are thought to be important in mediating tissue damage in inflammatory bowel disease (IBD). Many of the in vivo activities of tumor necrosis factor alpha (TNF-alpha) match the changes found in IBD, but its importance is controversial. METHODS:A sensitive, reverse hemolytic plaque assay was us...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(94)90398-0
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND & AIMS:We assessed the influence of genetic variants in the hepatitis B virus (HBV) core, which is a principal immunologic target, on the progression to hepatocellular carcinoma (HCC) in a cohort of 4841 male HBV carriers followed up for 16 years. METHODS:First, baseline sera from 116 HCC cases and 154 cont...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2009.07.063
更新日期:2009-11-01 00:00:00
abstract::We have examined the possibility that the 33- and 39-amino acid forms of cholecystokinin (CCK) are cleaved to produce CCK-octapeptide (CCK-8) during circulation in humans. When a mixture of the 33- and 39-amino acid forms of porcine CCK was infused at 0.1-2.5 pmol/kg.min into normal subjects, material indistinguishabl...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(88)90303-4
更新日期:1988-07-01 00:00:00
abstract:BACKGROUND & AIMS:Biliary atresia (BA) is a rare disease in infants, with unknown mechanisms of pathogenesis. It is characterized by hepatobiliary inflammatory, progressive destruction of the biliary system leading to liver fibrosis, and deterioration of liver function. Interleukin (IL) 17A promotes inflammatory and au...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2015.09.008
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND & AIMS:Helicobacter pylori infection causes inflammation, accumulation of reactive oxygen species, and oxidative DNA damage in the gastric mucosa. Apurinic/apyrimidinic endonuclease-1 (APE-1)/redox factor-1 (Ref-1) repairs damaged DNA and reductively activates transcription factors, including activator prote...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2004.06.017
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND & AIMS:Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS:...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1053/j.gastro.2019.05.056
更新日期:2019-09-01 00:00:00
abstract::To identify prognostic factors in cirrhotic patients admitted to the hospital for the treatment of an episode of ascites, a survival analysis was performed in a series of 139 patients hospitalized in our Unit between 1980 and 1985. Mean follow-up was 12.8 +/- 14.2 mo (mean +/- SD). A total of 38 variables based on his...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(88)90441-6
更新日期:1988-02-01 00:00:00
abstract:BACKGROUND & AIMS:Infection with Tropheryma whipplei has a range of effects-some patients can be chronic carriers without developing any symptoms, whereas others can develop systemic Whipple disease, characterized by a lack a protective inflammatory immune response. Alterations in HLA-G function have been associated wi...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2018.07.034
更新日期:2018-11-01 00:00:00