Tribbles 3 - a novel regulator of TLR2-mediated signaling in response to Helicobacter pylori lipopolysaccharide
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE25155 | GEO | 2011/01/12
SECONDARY ACCESSION(S): PRJNA134341
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE25146: Changes in gene expression in AGS cells in response to Helicobacter pylori lipopolysaccharide GSE25147: Changes in gene expression in MKN45 cells in response to Helicobacter pylori lipopolysaccharide GSE25148: Changes in gene expression in HEK-TLR2 cells in response to Helicobacter pylori lipopolysaccharide Refer to individual Series
2011-01-12 | E-GEOD-25155 | biostudies-arrayexpress
Project description:This study set out to identify global changes in gene expression in human embryonic kidney (HEK) cells stably transfected with Toll-like receptor 2 (TLR2) over a 48 hour time-course, following stimulation with 10 μg/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori. Microarray analysis was used to compare changes in gene expression between cells treated with 10 μg/ml H. pylori LPS and untreated cells at the same time point.
2011-01-12 | GSE25148 | GEO
Project description:This study set out to identify global changes in gene expression in human embryonic kidney (HEK) cells stably transfected with Toll-like receptor 2 (TLR2) over a 48 hour time-course, following stimulation with 10 μg/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori. Microarray analysis was used to compare changes in gene expression between cells treated with 10 μg/ml H. pylori LPS and untreated cells at the same time point. Total RNA was harvested from HEK-TLR2 cells following treatment with LPS for 2, 4, 8, 24 and 48h or untreated cells at the same time-point. 2 independent experiments were carried out. RNA was labeled and hybridized to GeneChips to analyse changes in gene expression.
2011-01-12 | E-GEOD-25148 | biostudies-arrayexpress
Project description:We have shown that Helicobacter pylori induces tolerogenic programming of dendritic cells and inhibits the host immune response. Toll-like receptors (TLRs) represent a class of transmembrane pattern recognition receptors essential for microbial recognition and control of the innate immune response. In this study, we examined the role of TLRs in mediating H. pylori tolerogenic programming of dendritic cells and their impact on anti-H. pylori immunity using C57BL/6 wild-type and TLR2-knockout (TLR2KO) mice. We analyzed the response of TLR2KO bone marrow-derived dendritic cells (BMDCs) to H. pylori SS1 stimulation and the outcome of chronic H. pylori infection in TLR2KO mice. We showed that H. pylori-stimulated BMDCs upregulated the expression of TLR2, but not TLR4, TLR5, or TLR9. H. pylori-stimulated BMDCs from TLRKO mice induced lower Treg and Th17 responses, but a higher IFN-γ response compared to H. pylori-stimulated BMDCs from wild-type mice. In vivo analyses following an H. pylori infection of 2 months duration showed a lower degree of gastric H. pylori colonization in TLR2KO mice and more severe gastric immunopathology compared to WT mice. The gastric mucosa of the infected TLR2KO mice showed a lower mRNA expression of Foxp3, IL-10, and IL-17A, but higher expression of IFN-γ compared to the gastric mRNA expression in infected wild-type mice. Moreover, the H. pylori-specific Th1 response was higher and the Treg and Th17 responses were lower in the spleens of infected TLR2KO mice compared to infected WT mice. Our data indicate that H. pylori mediates immune tolerance through TLR2-derived signals and inhibits Th1 immunity, thus evading host defense. TLR2 may be an important target in the modulation of the host response to H. pylori.
| S-EPMC3772856 | biostudies-literature
Project description:The increasing antibiotic resistance evolved by Helicobacter pylori has alarmingly reduced the eradication rates of first-line therapies. To overcome the current circulating resistome, we selected a novel potential therapeutic target in order to identify new candidate drugs for treating H. pylori infection. We screened 1120 FDA-approved drugs for molecules that bind to the essential response regulator HsrA and potentially inhibit its biological function. Seven natural flavonoids were identified as HsrA binders. All of these compounds noticeably inhibited the in vitro DNA binding activity of HsrA, but only four of them, apigenin, chrysin, kaempferol and hesperetin, exhibited high bactericidal activities against H. pylori. Chrysin showed the most potent bactericidal activity and the most synergistic effect in combination with clarithromycin or metronidazole. Flavonoid binding to HsrA occurs preferably at its C-terminal effector domain, interacting with amino acid residues specifically involved in forming the helix-turn-helix DNA binding motif. Our results validate the use of HsrA as a novel and effective therapeutic target in H. pylori infection and provide molecular evidence of a novel antibacterial mechanism of some natural flavonoids against H. pylori. The results further support the valuable potential of natural flavonoids as candidate drugs for novel antibacterial strategies.
| S-EPMC6683298 | biostudies-literature
Project description:Helicobacter pylori (H. pylori) is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating H. pylori. Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against H. pylori remains unclear. In the present study, in the co-culture model of macrophages with H. pylori, the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to H. pylori. Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by H. pylori. Clinical specimens showed that the number of Jagged1+ macrophages in the stomach mucosa from H. pylori-infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against H. pylori and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against H. pylori, but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against H. pylori, which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of H. pylori infection.
| S-EPMC8297740 | biostudies-literature
Project description:The small, regulatory RNA RepG (Regulator of polymeric G-repeats) regulates the expression of the chemotaxis receptor TlpB in Helicobacter pylori by targeting a variable G-repeat in the tlpB mRNA leader. Here, we show that RepG additionally controls lipopolysaccharide (LPS) phase variation by also modulating the expression of a gene (hp0102) that is co-transcribed with tlpB. The hp0102 gene encodes a glycosyltransferase required for LPS O-chain biosynthesis and in vivo colonization of the mouse stomach. The G-repeat length defines a gradual (rather than ON/OFF) control of LPS biosynthesis by RepG, and leads to gradual resistance to a membrane-targeting antibiotic. Thus, RepG-mediated modulation of LPS structure might impact host immune recognition and antibiotic sensitivity, thereby helping H. pylori to adapt and persist in the host.
| S-EPMC8295292 | biostudies-literature
Project description:This study set out to identify global changes in gene expression in MKN45 gastric epithelial cells following 8 hours stimulation with 10 μg/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori. Microarray analysis was used to compare changes in gene expression between cells treated with 10 μg/ml H. pylori LPS and untreated cells at the same time point.
2011-01-12 | GSE25147 | GEO
Project description:This study set out to identify global changes in gene expression in AGS gastric epithelial cells following 8 hours stimulation with 10 μg/ml lipopolysaccharide (LPS) from the gastric pathogen H. pylori. Microarray analysis was used to compare changes in gene expression between cells treated with 10 μg/ml H. pylori LPS and untreated cells at the same time point.
2011-01-12 | GSE25146 | GEO
Project description:The lipopolysaccharide O-antigen structure expressed by the European Helicobacter pylori model strain G27 encompasses a trisaccharide, an intervening glucan-heptan and distal Lewis antigens that promote immune escape. However, several gaps still remain in the corresponding biosynthetic pathway. Here, systematic mutagenesis of glycosyltransferase genes in G27 combined with lipopolysaccharide structural analysis, uncovered HP0102 as the trisaccharide fucosyltransferase, HP1283 as the heptan transferase, and HP1578 as the GlcNAc transferase that initiates the synthesis of Lewis antigens onto the heptan motif. Comparative genomic analysis of G27 lipopolysaccharide biosynthetic genes in strains of different ethnic origin revealed that East-Asian strains lack the HP1283/HP1578 genes but contain an additional copy of HP1105 and JHP0562. Further correlation of different lipopolysaccharide structures with corresponding gene contents led us to propose that the second copy of HP1105 and the JHP0562 may function as the GlcNAc and Gal transferase, respectively, to initiate synthesis of the Lewis antigen onto the Glc-Trio-Core in East-Asian strains lacking the HP1283/HP1578 genes. In view of the high gastric cancer rate in East Asia, the absence of the HP1283/HP1578 genes in East-Asian H. pylori strains warrants future studies addressing the role of the lipopolysaccharide heptan in pathogenesis.
| S-EPMC6892558 | biostudies-literature