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

In Helicobacter pylori infection both bacterial and host factors contribute to gastroduodenal mucosal damage. Indirect damage will result from the persistent innate and specific inflammatory response induced by bacterial products and the alterations in gastric physiology associated with infection. Cytokines play a critical role in the initiation and modulation of gastrointestinal inflammation. The gastric epithelium, which secretes chemokines in response to H. pylori, has a role in initiating acute inflammation. Bacterial induction of epithelial chemokines such as IL-8 involves protein tyrosine phosphorylation and NF-kappaB activation. Multiple genes in the cag pathogenicity island are essential for induction of epithelial chemokines. In vivo infection with cag-positive strains is associated with increased mucosal chemokines and inflammatory responses. Th1 cell-mediated responses characterized by interferon-gamma-secreting effector cells are also associated with increased mucosal inflammation. Variations in the magnitude and characteristics of the host cytokine responses induced by H. pylori are considered important factors determining the degree of chronic inflammation.
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PMID:Role of cytokines in pathogenesis of Helicobacter pylori-induced mucosal damage. 975 26

Recently, the relative contributions of local T helper cell responses of the Th1-type and Th2-type to the pathogenesis of gastritis and peptic ulcers associated with Helicobacter pylori infection have been examined. However, the results were controversial with respect to whether cellular immunity (Th1-type) or humoral immunity (Th2-type) responses predominate in H. pylori infection and with respect to how these responses may contribute to disease pathogenesis. In this study, we investigated the characteristics of the production of various cytokines induced by H. pylori or lipopolysaccharide (LPS), which was derived from H. pylori or Escherichia coli, in human peripheral blood mononuclear cells (PBMC). Live H. pylori induced production of many cytokines, such as IL-1beta, IL-10, IL-8, IFN-gamma, and TNF-alpha, whereas we could not detect IL-2 or IL-4. Moreover, we evaluated the effect of rebamipide on the production of several cytokines from PBMC induced by various stimuli. Rebamipide suppressed the production of IL-8, IL-10, TNF-alpha, and IL-1beta induced by H. pylori in a dose-dependent manner. On the other hand, the production of IL-12 induced by H. pylori showed a tendency to increase as a result of treatment of the cells with rebamipide. These results suggested that rebamipide might be effective in regulating cytokine responses in the H. pylori-infected host and maintaining host immunity. Moreover, it might contribute positively to disease progression and bacterial eradication.
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PMID:Effects of rebamipide on production of several cytokines by human peripheral blood mononuclear cells. 975 44

Interleukin-8 (IL-8) may play an important role in Helicobacter pylori infection-associated chronic active gastritis and peptic ulcer disease in human. We have recently reported that a gastric cancer cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori. Moreover, H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription. In this study, we evaluated the effect of rebamipide, an antigastritis and antiulcer agent, on H. pylori-induced IL-8 production. Rebamipide inhibited the production of IL-8 in several gastric cancer cell lines infected with H. pylori. In addition, rebamipide suppressed H. pylori-induced IL-8 gene expression at the transcriptional level as revealed by northern blotting analysis and luciferase activity in cells that were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44). Furthermore, rebamipide significantly suppressed the NF-kappaB activation by H. pylori infection. These results suggest that rebamipide may protect against the mucosal inflammation associated with H. pylori infection through inhibition of a proinflammatory cytokine, IL-8.
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PMID:Molecular analysis of suppression of interleukin-8 production by rebamipide in Helicobacter pylori-stimulated gastric cancer cell lines. 975 46

Nitric oxide produced by inducible nitric oxide synthase (iNOS) has been claimed to be involved in gastritis; however, its characteristics are largely unknown. We assessed (1) iNOS expression in the human gastric mucosa in chronic gastritis and (2) the cytokines associated with iNOS expression. Gastric biopsy specimens were obtained from patients with chronic gastritis. Total RNA was isolated and reverse transcription-polymerase chain reaction (PCR) was performed semiquantitatively using specific primer sets for iNOS, interleukin (IL)-1beta, IL-8, IL-6, interferon-y, tumor necrosis factor-alpha (TNF-alpha), TNF receptors, IL-6 receptors, and sucrase, respectively. Helicobacter pylori infection was examined by the PCR assay. Reverse transcription-PCR analysis showed that expression of iNOS was detected in 10 of 23 samples. Expression of iNOS mRNA was closely correlated with expression of TNF-alpha and was observed frequently in subjects with intestinal metaplasia. The Helicobacter pylori gene was detected by PCR assay in all iNOS-positive cases. These results indicate that iNOS is predominantly expressed in the gastric mucosa with intestinal metaplasia and H. pylori infection. TNF-alpha is thought to be an important cytokine associated with iNOS expression.
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PMID:Enhanced expression of inducible nitric oxide synthase in chronic gastritis with intestinal metaplasia. 980 53

The host immune response to Helicobacter pylori infection might be of importance with regard to the outcome of infection by this organism, e.g., to explain why only a proportion of infected subjects develop peptic ulcers. In this study we have analyzed the local response of different cytokines-i.e., the proinflammatory interleukin-1beta, (IL-1beta), IL-6, tumor necrosis factor alpha, and IL-8; the immunoregulatory gamma interferon (IFN-gamma); and IL-4; and the anti-inflammatory transforming growth factor beta (TGF-beta)-in antral biopsy specimens from H. pylori-infected duodenal ulcer (DU) patients and asymptomatic (AS) carriers (i.e., with chronic gastritis only). For comparison, biopsy specimens from uninfected healthy individuals were also analyzed. An immunohistochemical technique was used to allow quantification of the cytokine responses as well as identification of the cell types associated with the cytokine expression. We found that the levels of all of the studied cytokines except IL-4 were increased in the H. pylori-infected subjects compared to the levels in the healthy individuals. Our results indicate that the antral cytokine response is of the Th1 type since IFN-gamma, but not IL-4, was up-regulated both in H. pylori-infected DU patients and in AS carriers. However, there were no significant differences in either proinflammatory or immunoregulatory cytokine levels when H. pylori-infected subjects with and without peptic ulcers were compared. Some of the cytokines, particularly IL-1beta and TGF-beta, were also found in the gastric mucosae of healthy, uninfected subjects. We also showed that the gastric epithelium contributes substantially to the antral cytokine response of the proinflammatory cytokines IL-1beta and IL-6 in addition to IL-8.
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PMID:Local cytokine response in Helicobacter pylori-infected subjects. 982 79

Interleukin-8 (IL-8) production by the gastric mucosa is increased in Helicobacter pylori infection. Previous studies indicated that H. pylori induces IL-8 synthesis in cancer cell lines, and the ability of H. pylori to stimulate IL-8 production is supposed to be associated with cagA and other cag pathogenicity island genes, including picB gene. In the present study, we investigated the induction of IL-8 in primary cultures of normal human gastric epithelial cells to elucidate the IL-8 induction by wild type strains and by the picB knockout strain. Human gastric epithelial cells were obtained from surgically resected specimens from four patients. Three H. pylori strains (TN2F4; type 1 clinical isolate, TN2F4m1; isogenic picB mutant of TN2F4, Tx30a; type 2 strain) were cocultured with the normal gastric epithelial cells or the transformed MKN-28. IL-8 levels in culture medium were determined by enzyme immunoassay. Human gastric epithelial cells produced IL-8 at a 10-50 times higher level than MKN-28 did when cocultured with TN2F4. The mutant TN2F4m1 induced IL-8 at significantly lower levels than the parent strain. Cells from four patients behaved similarly on IL-8 production. The results of the present study demonstrated the induction of IL-8 in normal gastric epithelial cells, suggesting that picB gene product may play an essential role in vivo.
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PMID:Interleukin-8 production in primary cultures of human gastric epithelial cells induced by Helicobacter pylori. 988 8

The effects of inflammatory cytokines induced by Helicobacter pylori infection on acid secretion have not been well defined. The purpose of this study was to investigate the direct effects of these cytokines on parietal cells isolated from guinea pigs. We examined the effects of human recombinant IL-1beta (0.05-100 ng/ml), IL-8 (2-256 ng/ml), and TNF-alpha (0.625-80 ng/ml) on acid secretion stimulated by three secretagogues (10(-4) M histamine, 10(-4) M carbachol, and 10(-5) M tetragastrin) and on basal acid secretion from isolated parietal cells, which was measured by the aminopyrine accumulation method. None of three cytokines showed any significant effects on stimulated or basal acid secretion from isolated guinea pig parietal cells. We concluded that inflammatory cytokines induced by Helicobacter pylori infection may affect acid secretion through mechanisms other than direct actions on parietal cells.
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PMID:Effects of inflammatory cytokines induced by Helicobacter pylori infection on aminopyrine accumulation in parietal cells isolated from guinea pigs. 1071 40

Gastric epithelial chemokine response is a primary factor in the induction of gastric inflammation associated with Helicobacter pylori infection. Because sustained inflammation is a risk for gastric mucosal damage, agents that down-regulate inflammatory responses may be of therapeutic significance. We examined the effect of polaprezinc, a potent antiulcer agent, on proinflammatory cytokine-induced interleukin (IL)-8 expression in gastric epithelial cells. Because IL-8 expression is regulated by the transcription factor nuclear factor-kappaB (NF-kappaB), we also examined the effect of polaprezinc on NF-kappaB activity. MKN28 cells were used as a model of gastric epithelial cells. Secreted IL-8 was quantified by IL-8 specific enzyme-linked immunosorbent assay, and IL-8 mRNA expression was examined by Northern blot analysis. NF-kappaB activity was analyzed by electrophoretic mobility shift assay. Western blot analysis with anti-phospho-IkappaB-alpha antibody was performed to assess IkappaB-alpha phosphorylation. Polaprezinc-suppressed IL-8 secretion induced by tumor necrosis factor alpha (TNF-alpha) or IL-1beta in a dose-dependent manner. IL-8 mRNA expression also was inhibited by polaprezinc. NF-kappaB activation in response to TNF-alpha, IL-1beta, phorbol ester, and H(2)O(2) was down-regulated by polaprezinc. Western blot analysis showed inhibition of TNF-alpha-induced IkappaB-alpha phosphorylation in the presence of polaprezinc. Collectively, these results suggest that polaprezinc is a novel type of anti-inflammatory agent that down-regulates inflammatory responses of gastric mucosal cells.
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PMID:Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor-kappaB activiation and interleukin-8 expression in gastric epithelial cells. 1049 Sep 23

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

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


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