UNIPROT:P10145 - FACTA Search

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Query: UNIPROT:P10145 (IL-8)
23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the steadily increasing occurrence of antibiotic resistance in bacteria, there is a great need for new antibacterial compounds. The approach described here involves targeting virulence-related bacterial type IV secretion systems (TFSSs) with small-molecule inhibitors. The cag TFSS of Helicobacter pylori was chosen as a model, and novel inhibitors directed against the cag VirB11-type ATPase Cagalpha were identified. The cag genes encode proteins that are components of a contact-dependent secretion system used by the bacterium to translocate the effector molecule CagA into host cells. Translocated CagA is associated with severe gastritis, and carcinoma. Furthermore, functional TFSSs and immunodominant CagA play a role in interleukin (IL)-8 induction, which is an important factor for chronic inflammation. Inhibitors of Cagalpha were identified by high-throughput screening of chemical libraries that comprised 524 400 small molecules. The ATPase activity of Cagalpha was inhibited by the selected compounds in an in vitro enzymic assay using the purified enzyme. The most active compound, CHIR-1, reduced TFSS function to an extent that cellular effects on AGS cells mediated by CagA were virtually undetectable, while reduced levels of IL-8 induction were observed. Gastric colonization by CHIR-1-pre-treated bacteria was found to be impaired in a dose-dependent manner using a mouse model of infection. Small-molecule Cagalpha inhibitors, the first described inhibitors of a TFSS, are potential candidates for the development of new antibacterial compounds that may lead to alternative medical treatments. The compounds are expected to impose weak selective pressure, since they target virulence functions. Moreover, the targeted virulence protein is conserved in a variety of bacterial pathogens. Additionally, TFSS inhibitors are potent tools to study the biology of TFSSs.
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PMID:Inhibitors of Helicobacter pylori ATPase Cagalpha block CagA transport and cag virulence. 1700 73

Our recent studies documented that red ginseng extract (RGE, isolates from steamed and dried Panax ginseng, C.A. Meyer) can inhibit Helicobacter pylori-induced mitogen-activated protein kinase (MAPK) signaling with repressing either nuclear factor (NF)-kappaB-DNA binding activity or releases of IL-8 and COX-2 in gastric epithelial cells (Dig Dis Sci 50:1218-1227, 2005). We extended the experiment to prove whether RGE influences 5-lipoxygenase (5-LOX) pathway, thereby suppressing the biosynthesis of 5(S)-HETE. The 5-LOX enzyme activities were measured by thin layer chromatography using (14)C-labeled arachidonic acid (AA) and quantified by reverse phase-high performance liquid chromatography in human gastric adenocarcinoma (AGS) cells cocultured with H pylori (ATCC 43504 strain) with or without pretreatment of RGE. Western blotting analyses for MAPK signaling and 5-LOX, reverse transcriptase polymerase chain reaction for interleukin-8, and electrophoretic mobility shift assay for NF-kappaB-DNA binding were done, respectively. H pylori infection increased exclusively 5-LOX enzyme activity and RGE inhibited H pylori-stimulated 5-LOX activity, resulting in suppression of 5(S)-HETE generations from AA. RGE inactivated c-jun phosphorylation and repressed redox-sensitive transcriptional activation, led to reduced expression of IL-8 and 5-LOX mRNA in gastric mucosal cells, of which action was very similar to known LOX inhibitor, 200 mumol of geraniin. RGE could be phytoceutical against H pylori infection-associated gastric inflammation through its LOX-inhibiting actions, inhibitory 5-LOX enzyme activity, and attenuating its expression.
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PMID:Inhibitory activities and attenuated expressions of 5-LOX with red ginseng in Helicobacter pylori-infected gastric epithelial cells. 1733 52

We examined the kinetics of IL-8 production and CagA status in AGS infected with Helicobacter pylori, 26695 (Western CagA-type), HPK5 (Eastern CagA-type) and isogenic cagA-disrupted mutants, exposed to different pH (pH 6 and pH 3). IL-8 was produced in the early and late phases after infection in CagA-dependent and -independent manners, respectively, irrespective of CagA-type. The wild-type exposed to low pH tremendously reduced IL-8 level at early phase, but restored with urea, suggesting that low pH exerted the kinetics of H. pylori-induced IL-8 production in CagA-dependent manner and urea was necessary for effective induction. CagA and phosphorylated CagA increased time-dependently after infection. Phosphorylated CagA from 26695, but not HPK5, rapidly peaked, consistent with the kinetics of IL-8 induction and appearance of hummingbird phenotype. ATF3 transcripts peaked late phase by wild-type, however, induced in two peaks early and late phases by cagA-disrupted mutants, indicating that different CagA-type proteins altered ATF3 induction in the infected cells.
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PMID:Relationship of IL-8 production and the CagA status in AGS cells infected with Helicobacter pylori exposed to low pH and activating transcription factor 3 (ATF3). 1744 33

To explore the interactions between the host, environment and bacterium responsible for the different manifestations of Helicobacter pylori infection, we examined the effect of acidic conditions on H. pylori-induced interleukin (IL)-8 expression. AGS gastric epithelial cells were exposed to acidic pH and infected with H. pylori[wild-type strain, its isogenic cag pathogenicity island (PAI) mutant or its oipA mutant]. Exposure of AGS cells to acidic pH alone did not enhance IL-8 production. However, following exposure to acidic conditions, H. pylori infection resulted in marked enhancement of IL-8 production which was independent of the presence of the cag PAI and OipA, indicating that H. pylori and acidic conditions act synergistically to induce gastric mucosal IL-8 production. In neutral pH environments H. pylori-induced IL-8 induction involved the NF-kappaB pathways, the extracellular signal-regulated kinase (ERK)-->c-Fos/c-Jun-->activating protein (AP-1) pathways, JNK-->c-Jun-->AP-1 pathways and the p38 pathways. At acidic pH H. pylori-induced augmentation of IL-8 production involved markedly upregulated the NF-kappaB pathways and the ERK-->c-Fos-->AP-1 pathways. In contrast, activation of the JNK-->c-Jun-->AP-1 pathways and p38 pathways were pH independent. These results might explain the clinical studies in which patients with duodenal ulcers had higher levels of IL-8 in the antral gastric mucosa than patients with simple H. pylori gastritis.
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PMID:Helicobacter pylori environmental interactions: effect of acidic conditions on H. pylori-induced gastric mucosal interleukin-8 production. 1751 62

Helicobacter pylori infection leads to gastroduodenal inflammation, peptic ulceration, gastric lymphoma and gastric cancer. Certain herbal remedies have been used to treat gastric disease. In this study, we examined the anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on Helicobacter pylori-infected human gastric epithelial AGS cell. AGS cells were treated with Helicobacter pylori at a bacterium/cell ratio of 300:1. mRNA expression and protein levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and western blot analysis, respectively. Interleukin-8 (IL-8) level and the translocation of nuclear factor kappa B (NF-kappaB) were measured by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked DNA-protein interaction assay (ELDIA), respectively. Nitric oxide production was measured by Griess reagent. We found that SHXT and baicalin inhibited Helicobacter pylori-induced cyclooxygenase-2 (COX-2) enhancement and IkappaBalpha degradation in both mRNA and protein levels. SHXT and baicalin also inhibited Helicobacter pylori-induced inducible nitric oxide synthase (iNOS) and IL-8 mRNA expression, and decreased NO and IL-8 production. Furthermore, SHXT and baicalin inhibited nuclear translocation of p50 subunit of NF-kappaB in Helicobacter pylori-infected AGS cells. Based on the above findings, SHXT and baicalin might exert anti-inflammatory and gastroprotective effects in Helicobacter pylori-induced gastric inflammation.
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PMID:San-Huang-Xie-Xin-Tang inhibits Helicobacter pylori-induced inflammation in human gastric epithelial AGS cells. 1753 3

Inflammatory processes are implicated in gastric cancer development. In contrast, the role of inflammation and proinflammatory cytokines in established cancer remains to be clarified. We investigated the contribution of IL-17A versus IL-17F-mediated intracellular signalling pathways in human gastric adenocarcinoma AGS cells. IL-8 secretion was evaluated by ELISA, mitogen-activated protein kinase (MAPK)(4) by Western blotting, and activator protein 1(AP-1) and nuclear factor kappa B (NFkappaB) by TransAM transcription factor assay or qRT-PCR. IL-17RA and IL-17RC inhibition were achieved by small interfering RNA (siRNA). IL-17A significantly induced activation of all three MAPK (ERK, p38 and JNK) and downstream transcription factors AP-1 and p65 NFkappaB. IL-17F was less potent but induced a significant activation of p65 NFkappaB. Consistently, IL-17A was more potent to induce IL-8 secretion than IL-17F. Inhibition of either IL-17RA or IL-17RC expression via siRNA led to near complete abrogation of IL-17A-mediated c-Jun and p65 activation. These data suggest that in gastric cancer, absence of either IL-17RA or IL-17RC can inhibit IL-17 responsiveness. Conversely, downstream of IL-17R binding, IL-17A and IL-17F induce key signal transduction pathways implicated in inflammation and carcinogenesis. IL-17A, and possibly IL-17F, may contribute to amplification and persistence of inflammatory processes implicated in inflammation-associated cancer.
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PMID:IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells. 1764 50

Helicobacter pylori infection is the most common cause of gastritis, gastric ulcer and adenocarcinoma. It has proven difficult to cure because of its capability to develop strains resistant to antibiotics. The effect of three strains of lactic acid bacteria (LAB) and bovine colostral preparations on the adhesion of H. pylori NCTC 11637 on gastric adenocarcinoma (AGS) cells and on the interleukin (IL)-8 production was studied. Before infection, H. pylori were pretreated with Lactobacillus plantarum MLBPL1, Lactobacillus rhamnosus GG, Lactococcus lactis, or with a colostral preparation with or without specific H. pylori antibodies. The relative number of H. pylori adhered on AGS cells was determined by urease test. IL-8 produced by the cells was studied by enzyme-linked immunosorbent assay. Colostral preparations with and without specific antibodies reduced the adhesion of H. pylori on AGS cells in a dose-dependent manner. Live LAB at a concentration of 10(10) CFU/ml reduced the adhesion by approximately 50% (P < 0.05). After the infection of AGS cells by H. pylori, the IL-8 level rose up to about 10-fold (5500 +/- 1600 pg/ml). Pretreatment of H. pylori with colostral preparations or high concentrations of LAB prevented this IL-8 rise. Similar effect was seen with live and heat-killed LAB, the live LAB being more effective. Heat-killed LAB at a concentration of 10(10) CFU/ml rose the IL-8 level of non-infected cells significantly. Suppression of IL-8 production by LAB or colostral products could have a suppressive effect on inflammation in Helicobacter infection.
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PMID:Effect of specific colostral antibodies and selected lactobacilli on the adhesion of Helicobacter pylori on AGS cells and the Helicobacter-induced IL-8 production. 1862 49

Helicobacter pylori strains from East Asia have an 'East Asian' type of CagA that is more active and predominantly comprises a single type. Strains from other countries have a 'western' type of CagA, which is less active and comprises many different types generated by intragenomic recombination. Co-culture of AGS gastric epithelial cells with isolates of western strains that displayed microevolution in CagA showed that isolates with additional copies of the C motif induced significantly more interleukin (IL)-8 secretion. Co-culture of AGS cells with western and East Asian strains, each expressing CagA with a single copy of the C or D motif, showed that East Asian strains induced significantly more IL-8 secretion. Analysis of the different CagA types from data deposited in GenBank and from the literature showed that western CagA is significantly more likely to undergo duplication of tyrosine phosphorylation motif C than East Asian CagA is of the corresponding D motif. Taken together, the data suggest that the already highly active East Asian CagA with one D motif has no requirement to increase its virulence, whereas the less active western CagA displays flexibility in its capacity to increase its number of tyrosine phosphorylation motifs to become more virulent.
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PMID:Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion. 1871 74

Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used broadly in the Mediterranean diet. We aimed to investigate the gastric cancer preventive activity of methanol extracts obtained from currants from three different origins in Greece (Vostizza, Nemea, and Messinia) as well as methanol extracts obtained from Sultanas cultivated in the island of Crete as to inhibition of cell proliferation, induction of apoptosis, and inhibition of inflammation. All extracts from 500 microg dried raisins studied suppressed cell proliferation, significantly those obtained from Sultanas from Crete and currants from Nemea. Flow cytometric analysis of Annexin-V labeled cells indicated that Cretan Sultana, Nemea, and Messinia currants at 500 microg dried product/ml medium significantly induced cell death. All extracts from 500 microg dried raisins statistically decreased protein and mRNA levels of ICAM-1 in TNF-alpha stimulated cells. Measurement of IL-8 protein levels and quantification for IL-8 mRNA showed no significant decrease. These results indicate that the methanol extracts from currants, rich in phenolic compounds, exhibit cancer preventive efficacy by limiting cell proliferation, inducing cell death, and suppressing ICAM-1 levels in AGS cells.
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PMID:Effect of Greek raisins (Vitis vinifera L.) from different origins on gastric cancer cell growth. 1900 79

In recent years, natural dietary agents have drawn a great deal of attention owing to their demonstrated ability to suppress cancer. We aimed to investigate the in-vitro gastric cancer preventive activity of a methanol extract obtained from table olives of Greek origin. Tested were AGS cell proliferation, induction of apoptosis and inhibition of inflammation. AGS stomach cancer cells were cultured at a density of 10 cells/ml. Methanol extract of olive was added to cultures at concentrations of 2.0, 1.6, 1.0, and 0.4 microg phenols/ml. Effect on cellular viability was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and percentages of early and late apoptotic cells were assayed by annexin V-FITC staining on a FACS scan. Interleukin-8 (IL-8) and intercellular adhesion molecule (ICAM)-1 mRNA and protein production were measured by applying reverse transcriptase-PCR and enzyme-linked immunosorbent assay. Olive extract significantly suppressed cell proliferation at 2.0, 1.6, and 1.0 microg phenols/ml. Flow cytometric analysis of Annexin-V labeled cells indicated that 2.0 microg phenols/ml significantly induced apoptosis. Similarly, at 2.0, 1.6, and 1.0 microg phenols/ml a significant decrease of ICAM-1 and IL-8 protein levels was observed. ICAM-1, as well as IL-8, mRNA expression were decreased in the presence of 2.0 microg phenols/ml. Results indicate that the methanol extract from olives, rich in phenolic compounds, exhibits gastric cancer preventive efficacy by limiting cell proliferation, inducing cell death and suppressing inflammation in AGS cells.
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PMID:In-vitro gastric cancer prevention by a polyphenol-rich extract from olives through induction of apoptosis. 1907 62

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