Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H. pylori whole genome microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several strain-specific differences in gene composition including a large deletion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection.
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PMID:Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses. 1123 62

Helicobacter pylori strains that possess the cag pathogenicity island induce more severe gastritis and augment the risk of developing peptic ulcer disease and distal gastric cancer. A specific mechanism by which cag(+) strains may enhance gastritis is strain-selective regulation of interleukin (IL)-8 production. On contact with gastric epithelial cells, H. pylori activates multiple signal transduction cascades that regulate IL-8 secretion, including nuclear factor-kappaB and mitogen-activated protein kinases, and these events are dependent on genes within the cag island. An independent effect of cag-mediated cellular contact is translocation and phosphorylation of H. pylori proteins within the host epithelial cell. The redundancy of intracellular signaling cascades activated by H. pylori and the divergent epithelial cell responses induced by components of the cag island may contribute to the ability of this organism to persist for decades within the gastric niche.
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PMID:IV. Helicobacter pylori strain-specific activation of signal transduction cascades related to gastric inflammation. 1125 77

Helicobacter pylori infection results in chronic gastritis, which is initiated by the release of cytokines like interleukin (IL)-12 and IL-8 from mononuclear cells, and IL-8 from gastric epithelial cells. The severity of gastritis is influenced both by host factors and by bacterial factors such as the Cag proteins and the vacuolating cytotoxin VacA. Amounts of IL-12 and IL-8 produced by monocytic THP-1 cells differed considerably between the eight H. pylori isolates tested, but in contrast to H. pylori-induced IL-8 production by gastric epithelial cells, did not correlate to the Cag and VacA types of the strains. Apparently, in addition to Cag and VacA, other bacterial factors determine the extent in which H. pylori induced IL production in monocytes.
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PMID:The role of Helicobacter pylori virulence factors in interleukin production by monocytic cells. 1126 85

The pathogenic role of human neutrophils has been implicated in Helicobacter pylori-associated gastritis. Ecabet sodium, a locally acting antiulcer drug, has anti-H. pylori actions. The aim of this study was to examine the effects of ecabet on the ability of H. pylori to stimulate human neutrophils. H. pylori were added to 1 x 10(5) neutrophils and incubated for 30 min in the presence of ecabet. Bacterial suspensions which had been incubated with ecabet for 30 min were also used to stimulate neutrophils. The intracellular production of reactive oxygen species was measured with a FACScan. Bacterial suspensions were also added to neutrophils in the presence of ecabet and incubated at 37 degrees C for 12 h to measure interleukin (IL)-8 production by enzyme-linked immunosorbent assay. The mean fluorescence intensity was found to be attenuated dose-dependently by ecabet (P < 0.01). Ecabet also inhibited IL-8 production by neutrophils in a dose-dependent manner (P < 0.001). Bacteria with prior incubation with ecabet induced significantly lower IL-8 production than those without this incubation (P < 0.05). Ecabet sodium has preventive effects on the ability of H. pylori to stimulate human neutrophils. It may lead to reduced gastritis activity and decreased oxidative damage of the gastric mucosa in H. pylori-associated gastritis.
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PMID:Ecabet sodium inhibits the ability of Helicobacter pylori to induce neutrophil production of reactive oxygen species and interleukin-8. 1129 77

The Helicobacter pylori chromosomal region known as the cytotoxin-gene associated pathogenicity island (cag PAI) is associated with severe disease and encodes proteins that are believed to induce interleukin (IL-8) secretion by cultured epithelial cells. The objective of this study was to evaluate the relationship between the cag PAI, induction of IL-8, and induction of neutrophilic gastric inflammation. Germ-free neonatal piglets and conventional C57BL/6 mice were given wild-type or cag deficient mutant derivatives of H. pylori strain 26695 or SS1. Bacterial colonization was determined by plate count, gastritis and neutrophilic inflammation were quantified, and IL-8 induction in AGS cells was determined by enzyme-linked immunosorbent assay. Deletion of the entire cag region or interruption of the virB10 or virB11 homolog had no effect on bacterial colonization, gastritis, or neutrophilic inflammation. In contrast, these mutations had variable effects on IL-8 induction, depending on the H. pylori strain. In the piglet-adapated strain 26695, which induced IL-8 secretion by AGS cells, deletion of the cag PAI decreased induction. In the mouse-adapted strain SS1, which did not induce IL-8 secretion, deletion of the cagII region or interruption of any of three cag region genes increased IL-8 induction. These results indicate that in mice and piglets (i) neither the cag PAI nor the ability to induce IL-8 in vitro is essential for colonization or neutrophilic inflammation and (ii) there is no direct relationship between the presence of the cag PAI, IL-8 induction, and neutrophilic gastritis.
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PMID:Role of Helicobacter pylori cag region genes in colonization and gastritis in two animal models. 1129 5

CXC chemokine receptor 1 (CXCR1) is one of the important receptors for CXC chemokines with ELR motif, of which interleukin 8 (IL-8; CXCL8) is representative. To identify the cell type(s) of CXCR1-expressing cells in inflamed stomach and gut tissues, we performed immunoperoxidase method using pre-fixed frozen sections. In chronic gastritis associated with Helicobacter pylori infection (7 cases), CXCR1 was positive in neutrophils (polymorphonuclear leucocytes) in the lamina propria near the neck region and those in pit abscess. In ulcerative colitis (6 cases) and Crohn's disease (5 cases), CXCR1 was sporadically expressed by neutrophils in the mucosa, and particularly CXCR1+ neutrophils were abundantly distributed in inflammatory granulation tissue in ulcer base. Double staining confirmed co-localization of CXCR1 and neutrophil elastase. Neither CD3+ T lymphocytes nor CD68+ macrophages were positive for CXCR1. Immunoelectron microscopy confirmed the cell surface localization of CXCR1. Neutrophils protect the host from microbial pathogens. However, they also cause damages to host tissues in chronic inflammation. Therefore, our study underscores the importance of CXCR1 expression in inflammatory processes.
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PMID:CXC chemokine receptor 1 (CXCR1) is expressed mainly by neutrophils in inflamed gut and stomach tissues. 1200 74

Increased gastric production of interleukin 8 and tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of Helicobacter pylori-associated gastroduodenal disease. In the present study we used a mouse model to demonstrate whether loss of the tumor necrosis factor receptor 1 (TNF-R1) function leads to differences in gastric inflammation or the systemic immune response in H. pylori infection. Six different clinical isolates of H. pylori (three cytotoxin-positive and three cytotoxin-negative strains) were adapted to C57BL/6 mice. TNF-R1-deficient (TNF-R1(-/-)) mice (n = 19) and isogenetic controls (n = 24) were infected and sacrificed after 4 weeks of infection. Inflammation of the stomach and the humoral immune response to H. pylori were evaluated by histological, immunohistochemical, and serological methods. There was no detectable difference in the grade or activity of gastritis in TNF-R1(-/-) mice when they were compared with wild-type mice, but the number of lymphoid aggregates was slightly reduced in the gastric mucosa of TNF-R1(-/-) mice. Interestingly, total immunoglobulin G (IgG), as well as IgG1, IgG2b, and IgG3, H. pylori-specific antibody titers were significantly higher in wild-type mice. As revealed by immunoblot analysis, the difference in reactivity against H. pylori antigens was not based on a failure to recognize single H. pylori antigens in TNF-R1(-/-) mice. We therefore suggest that TNF-R1-mediated TNF-alpha signals might support a systemic humoral immune response against H. pylori and that the gastric inflammatory response to H. pylori infection seems to be independent of TNF-R1-mediated signals.
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PMID:Role of tumor necrosis factor alpha in Helicobacter pylori gastritis in tumor necrosis factor receptor 1-deficient mice. 1201 Oct 9

Gastric Helicobacter pylori infection may lead to multifocal atrophic corpus gastritis associated with loss of epithelial cells as well as glandular structures. The current work investigated H. pylori effects on cell death of isolated, nontransformed rat parietal cells (PC). Highly enriched rat PC (>97%) were isolated from gastric mucosa and cultured in serum-free medium over 24 h. The cells were cocultured over 8 h with cytotoxin-associated immunodominant protein (cagA)(+)/vacuolating toxin (vacA)(+) or with cagA(-)/vacA(-) H. pylori laboratory strains and also with H. pylori mutants deleted in several genes of the cag pathogenicity island. Staphylococcus aureus or Campylobacter jejuni were used as controls. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and electron microscopy. Interleukin (IL)-8 and cytokine-induced neutrophil chemoattractant (CINC)-1 secretion was measured by ELISA. Activation of nuclear factor-kappaB (NF-kappaB) was studied in nuclear extracts of PC by electrophoretic mobility shift assay. Apoptosis of PC was induced in a concentration- and time-dependent manner by cagA(+)/vacA(+) H. pylori strains but not by cagA(-)/vacA(-) negative strains or by the cagE knockout mutant. S. aureus and C. jejuni had no effect. PC showed no IL-8 or CINC-1 secretion on exposure to cagA(+)/vacA(+) H. pylori. cagA(+)/vacA(+) strains induced activation of NF-kappaB complexes in nuclear extracts of PC, which were composed of p65 and p50 subunits. No significant stimulation of NF-kappaB activation was detected by incubation of PC with the cagE knockout mutant. Preincubation of PC with antisense but not missense oligodeoxynucleotides against the p65 subunit significantly reduced DNA binding to the kappaB recognition sequence. The p65 oligonucleotides as well as the proteasome inhibitor N-CBZ-isoleucin-glutamin-(o-t-butyl-)-alanin-leucin and the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine completely prevented PC apoptosis induced by cagA(+)/vacA(+) strains. In summary, cagE presence appears to be essential for H. pylori-induced apoptosis of gastric parietal cells, and this effect is dependent on the activation of NF-kappaB and production of nitric oxide.
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PMID:Helicobacter pylori induces apoptosis of rat gastric parietal cells. 1212 77

Methylation of bacterial DNA can regulate microbial growth and virulence. Expression of hpyIM, a conserved methyltransferase of the gastric pathogen Helicobacter pylori, was quantitated in gastric biopsy specimens from 41 H. pylori-infected patients and during growth in vitro, by quantitative reverse transcriptase-polymerase chain reaction and/or RNA slot-blot analysis, to determine whether levels of transcription were associated with pathologic outcome, as based on both severity of gastritis and inflammatory cytokine levels, or were regulated by bacterial growth phase. The effects that hpyIM inactivation has on bacterial morphology were determined by electron microscopy. Expression of hpyIM varied dramatically within colonized gastric tissue, and levels were not related to either colonization density, severity of inflammation, mucosal IL-8 concentrations, or clinical disease. In vitro, hpyIM expression was higher during log-phase growth and was required for normal bacterial morphology, suggesting that hpyIM expression may be growth-phase regulated within the gastric niche.
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PMID:Characterization of expression of a functionally conserved Helicobacter pylori methyltransferase-encoding gene within inflamed mucosa and during in vitro growth. 1235 74

This study was carried out to evaluate the prevalence and clinical characterizations of gastric Helicobacter spp. infection of dogs and cats in Korea. The prevalence of Helicobacter spp. infection of dogs and cats determined by urease test was 78.4% and 64%, respectively, although Helicobacter genus-specific PCR assay showed that it was 82.3% and 84%. Urease mapping results based on urease test showed that total positive rate of tested tissues from clinically abnormal dogs was significantly higher than that from clinically normal dogs (p=0.0018; Odds ratio = 6.118; 95% Confidence Interval = 1.96-19.103). These findings were consistent with the results of Helicobacter genus-specific PCR assay which showed that positive rate of the fundus (100%) and the antrum (100%) of clinically abnormal dogs was significantly higher than that of same gastric regions of clinically normal dogs (77.5 and 67.5% respectively). In comparison of gastric regions between clinically normal dogs and abnormal dogs, positive rate of urease test for the fundus (100%) and body (90.9%) in clinically abnormal dogs was significantly higher than that of abnormal dogs (72.5% and 57.5% respectively; p<0.05). The results of urease mapping in dogs and cats also indicated that Helicobacter colonization in the fundus was more dense compared with the density in the body and antrum. In Helicobacter species-specific PCR assay for dogs, 32 of 42 fundic tissues (76.2%) were positive for H. heilmannii and two (4.8%) were positive for H. felis. In cats, 18 of 21 fundic tissues (85.7%) were positive for H. heilmannii and 2 (9.5%) were positive for H. felis. Gastritis scores of fundic tissues from clinically abnormal infected dogs were similar to that from noninfected dogs and evidence of upregulation of IL-1beta, IL-8, and TNF-alpha mRNA was not detected in gastric fundic tissues from clinically abnormal infected dogs. This study suggested that Helicobacter spp. infection in domestic dogs including private owned pet dogs and cats is highly prevalent usually with no clinical sign but high density of colonization can be related to gastrointestinal signs
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PMID:Prevalence and clinical characterization of gastric Helicobacter species infection of dogs and cats in Korea. 1244 82


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