The role of CTH in the innate immune response to H. pylori
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE158817 | GEO | 2022/05/18
REPOSITORIES: GEO
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Project description:Macrophages play a crucial role in the inflammatory response to the human stomach pathogen Helicobacter pylori, which infects half of the world's population and causes gastric cancer. Recent studies have highlighted the importance of macrophage immunometabolism in their activation state and function. We have demonstrated that the cysteine-producing enzyme, cystathionine g-lyase (CTH), is upregulated in humans and mice with H. pylori infection. Here we show that induction of CTH in macrophages by H. pylori promotes persistent inflammation. Cth-/- mice have reduced macrophage and T-cell activation in H. pylori-infected tissues, an altered metabolome, and decreased enrichment of immune-associated gene networks, culminating in decreased H. pylori-induced-gastritis. CTH is downstream of the proposed anti-inflammatory molecule, S-adenosylmethionine (SAM). While Cth-/- mice exhibit gastric SAM accumulation, WT mice treated with SAM did not display protection against H. pylori-induced inflammation. Instead, we demonstrate that Cth-deficient macrophages exhibit alterations in the proteome, decreased NF-kB activation, diminished expression of macrophage activation markers, and impaired oxidative phosphorylation and glycolysis. Thus, through altering cellular respiration, CTH is a key enhancer of macrophage activation contributing to a pathogenic inflammatory response that is the universal precursor for the development of H. pylori-induced gastric disease.
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2011-09-07 | E-GEOD-31991 | biostudies-arrayexpress
Project description:Helicobacter pylori are gram-negative bacteria that colonize the human stomach and are the major etiological factor in gastric carcinoma development. The aim of this work was to evaluate changes in gene expression in gastric cells induced by H. pylori.
2016-03-01 | GSE70394 | GEO
Project description:RNA sequencing by Illumina NovaSeq6000 was performed on gastric tissues of Odc fl/fl and Odc_Delta_Epi mice infected or not with H. pylori PSS1 for 4 weeks to determine the role of epithelial ODC in H. pylori pathogenesis
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Project description:Helicobacter pylori are gram-negative bacteria that colonize the human stomach and are the major etiological factor in gastric carcinoma development. The aim of this work was to evaluate changes in gene expression in gastric cells induced by H. pylori. The human gastric carcinoma-derived cell line AGS was infected with H. pylori strain 60190 (ATCC 49503) for 24 hours. RNA was extracted from three independent experiments.
2016-03-01 | E-GEOD-70394 | biostudies-arrayexpress
Project description:Helicobacter pylori colonization of the human stomach is a strong risk factor for gastric cancer. To investigate H. pylori-induced gastric molecular alterations, we used a Mongolian gerbil model of gastric carcinogenesis. Histologic evaluation revealed varying levels of atrophic gastritis (a premalignant condition characterized by parietal and chief cell loss) in H. pylori-infected animals, and transcriptional profiling revealed a loss of markers for these cell types. We then assessed the spatial distribution and relative abundance of proteins in the gastric tissues using imaging mass spectrometry and liquid chromatography with tandem mass spectrometry (LC-MS/MS). We detected striking differences in protein content of corpus and antrum tissues. 492 proteins were preferentially localized to the corpus in uninfected animals. The abundance of 91 of these proteins was reduced in H. pylori-infected corpus tissues exhibiting atrophic gastritis compared to infected corpus tissues with non-atrophic gastritis or uninfected corpus tissues; these included numerous proteins with metabolic functions. Fifty proteins localized to the corpus in uninfected animals were diffusely delocalized throughout the stomach in infected tissues with atrophic gastritis; these included numerous proteins with roles in protein processing. Corresponding alterations were not detected in animals infected with a H. pylori ∆cagT mutant (lacking Cag type IV secretion system activity). These results indicate that H. pylori can cause loss of proteins normally localized to the gastric corpus as well as diffuse delocalization of corpus-specific proteins, resulting in marked changes in the normal gastric molecular partitioning into distinct corpus and antrum regions.
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Project description:Helicobacter pylori (H. pylori) infection and excessive salt intake are known as important risk factors for stomach cancer in humans. However, interactions of these two factors with gene expression profiles during gastric carcinogenesis remain unclear. In this study, we established a mouse gastric tumor model combining a chemical carcinogen, H. pylori infection and a high-salt diet. The tumor incidence and multiplicity in N-methyl-N-nitrosourea-treated mice were significantly increased by combination of H. pylori with a high-salt diet. In addition, detailed examination indicated that excessive salt could regulate progression of gastric tumor. Global gene expression profiles in glandular stomach of the mouse model were investigated by cDNA microarray analysis, and 36 and 31 more than twofold up-regulated and down-regulated genes, respectively, were detected in the H. pylori-infection and high-salt diet combined group compared with the other groups. Quantitative RT-PCR confirmed significant over-expression of several candidate genes including Cd177, Reg3g, and Muc13. These results suggest that our mouse model combined with H. pylori infection and high-salt diet is useful for gene expression profiling in gastric carcinogenesis.
2011-05-25 | GSE29444 | GEO
Project description:Gene expression was studied in samples from the stomach of Rhesus monkeys that have been infected with Helicobacter pylori and treated with a known carcinogen (Ethyl-nitro-nitrosoguanidine (ENNG)) that is similar to known nitrosamine dietary carcinogens. The samples represent the following: Biopsy 4689 is from animal 81G taken 55 months after inoculation with H. pylori and the start of the carcinogen ENNG Biopsy 4691 is from animal 63G taken 55 months after inoculation with H. pylori and the start of the carcinogen ENNG Biopsy 4709 is from animal 92F taken after 55 months of observation and no treatment (control). Gastric biopsies were obtained at the indicated times and RNA was harvested from the sample. All hybridizations were conducted against a common reference that was prepared using commercially obtained RNA isolated from the stomach of uninfected monkeys. Infection: Inoculated with H. pylori and treated with carcinogen ENNG (Treated) or control
2013-06-07 | E-GEOD-38586 | biostudies-arrayexpress
Project description:Gene expression was studied in samples from the stomach of Rhesus monkeys that have been infected with Helicobacter pylori and treated with a known carcinogen (Ethyl-nitro-nitrosoguanidine (ENNG)) that is similar to known nitrosamine dietary carcinogens. The samples represent the following: Biopsy 4689 is from animal 81G taken 55 months after inoculation with H. pylori and the start of the carcinogen ENNG Biopsy 4691 is from animal 63G taken 55 months after inoculation with H. pylori and the start of the carcinogen ENNG Biopsy 4709 is from animal 92F taken after 55 months of observation and no treatment (control). Gastric biopsies were obtained at the indicated times and RNA was harvested from the sample. All hybridizations were conducted against a common reference that was prepared using commercially obtained RNA isolated from the stomach of uninfected monkeys.
2013-06-07 | GSE38586 | GEO
Project description:This experiment set contains the raw data for 8 arrays that were used in the genomic typing of the pre- and post-mouse H. pylori strains SS1 and SS2000. 10700 is the pre-mouse clinical isolate of SS1 and PMSS2000 is the pre-mouse clinical isolate of SS2000. gDNA from these strains were labeled and hybridized to H. pylori microarrays as described in Salama et al. {Salama et al. 2000 PNAS 97:14668-73}. In each case the test gDNA sample was labeled with Cy5 (red) and this was hybridized with Cy3 (green) labeled reference DNA of equal amount. The reference DNA consisted of equal amounts of gDNA from the two H. pylori strains used to make the H. pylori microarray, 26695 and J99. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
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