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)

Infection of the gastric antrum by Helicobacter pylori is characterised by a cellular inflammatory infiltrate. Whether cytokines are involved in the pathogenesis of this gastritis has been investigated by studying the effect of eradicating H pylori on the expression of genes encoding the cytokines interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) in the antral mucosa. Gastric antral biopsy specimens were taken from nine patients with duodenal ulcers and cytokine transcripts were identified and quantified by northern blotting. After H pylori had been eradicated the chronic inflammatory infiltrate decreased in all the patients and the polymorphonuclear infiltrate virtually disappeared. Expression of genes also decreased. After eradication, the median TNF-alpha mRNA/rRNA fell to 48% (p = 0.02) and the median IL-8 mRNA/rRNA fell to 5% (p = 0.004) of initial values. These results support the role of increased synthesis of these cytokines in the pathogenesis of the gastritis.
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PMID:Cytokine gene expression in Helicobacter pylori associated antral gastritis. 782 74

Gastric infection with Helicobacter pylori is frequently characterized by neutrophil infiltration. The production of the neutrophil-activating peptide (NAP-1/IL-8) and mucosal IgA autoantibodies to IL-8 by human antral biopsies have been examined during short-term in vitro culture. Detectable IL-8 was secreted by 84% of H. pylori-negative patients with normal antral mucosa (range < 0.07-61.5 ng/mg biopsy protein, n = 19). Concentrations in 4 patients with reactive gastritis and 10 with inactive gastritis were not significantly different from subjects with normal mucosa. In H. pylori-positive patients with active gastritis and neutrophil infiltration into the epithelium (n = 17) IL-8 secretion was significantly increased relative to subjects with normal mucosa (P < 0.0001), inactive gastritis (P < 0.001) and reactive gastritis (P < 0.01). IL-8 concentrations in active gastritis were significantly correlated with the extent of epithelial surface degeneration (r = 0.64). IgA autoantibodies were present in 19 patients (13 active, 4 inactive gastritis) and concentrations were significantly correlated with IL-8 production (P < 0.001). Gastric synthesis of IL-8 is likely to be an important factor in regulating mucosal neutrophil infiltration and activation in patients with H. pylori infection. The local production of IgA antibodies to IL-8 may represent a down-regulatory response of the host to limit mucosal damage associated with a chronic bacterial infection.
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PMID:Gastric interleukin-8 and IgA IL-8 autoantibodies in Helicobacter pylori infection. 841 74

In 10 patients with Helicobacter pylori (HP) positive chronic gastritis, gastric mucosal content of interleukin (IL)-1 beta, IL-8, Transforming Growth Factor (TGF)-beta 1, Epidermal Growth Factor (EGF) and Polyamines (putrescine, spermine and spermidine) was evaluated before and after eradicating treatment. Histologically, in all patients eradication of HP was accompanied by a marked reduction of the inflammatory infiltrate. At the same time, at the end of the therapeutical regimen, elevated levels of IL-1 beta, IL-8, TGF-beta 1, putrescine and spermidine/spermine ratio significantly dropped, while EGF mucosal content, significantly increased. Results are discussed in terms of the reciprocal role of inflammatory cytokines, growth factors and polyamines in the evolution of the HP-associated chronic gastritis.
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PMID:Successful eradicating treatment of Helicobacter pylori in patients with chronic gastritis: gastric levels of cytokines, epidermal growth factor and polyamines before and after therapy. 868 31

Approximately 60% of Helicobacter pylori strains are cagA+ and this genotype is more frequently associated with duodenal ulcer disease. Although most wild-type cagA+ strains are both cytotoxigenic and induce enhanced Interleukin-8 (IL-8) secretion in gastric epithelial cells, isogenic cagA- mutants retain full activity in these assays; thus, cagA appears to be a marker of enhanced virulence. Delineation of the nucleotide sequence of a 4 kb region upstream of cagA allowed the identification of 966 bp (picA) and 2655 bp (picB) open reading frames encoding 36 kDa and 101 kDa polypeptides, respectively. picA and picB constitute an operon in opposite orientation to cagA. The deduced picB product showed significant homology (26% identity and 50% similarity) with the Bordetella pertussis toxin secretion protein (PtlC). Of 55 H. pylori clinical isolates, the picA and picB segment was conserved exclusively in cagA+ strains and present in all isolates from patients with duodenal ulceration, versus 59% of isolates from patients with gastritis alone (P = 0.01). Using gene-replacement techniques, we constructed picA and picB mutant H. pylori strains and demonstrated that the picB gene product is involved in the induction of IL-8 expression in gastric epithelial cells. Further, Northern blot hybridization and RT-PCR data showed that picA and picB are co-transcribed and an insertional mutation in picA ablates picB expression. These studies indicate a role of picA and picB in the induction of an inflammatory response in gastric epithelial cells either directly or by enabling secretion of an unidentified product, and suggest a mechanism for the overrepresentation of strains possessing these genes in patients with peptic ulceration.
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PMID:Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells. 882 91

There have been few studies of cytokine expression in the gastric mucosa of patients with chronic gastritis. In the present study, to elucidate the expression of cytokines in the gastric mucosa and the immunopathological roles played by these cytokines in chronic gastritis, we investigated cytokine gene expression, by reverse transcription polymerase chain reaction, in gastric biopsy specimens obtained from 29 endoscopically normal patients with chronic gastritis. The cytokines examined and the mRNA positivity were: interleukin (IL)-1 beta (21%), IL-2 (0%), IL-3 (7%), IL-4 (41%), IL-5 (17%), IL-6 (53%), IL-8 (98%), interferon gamma (IFN-gamma) (69%), and tumor necrosis factor alpha (TNF-alpha) (24%). Although the histological severity of the gastritis was closely associated with Helicobacter pylori infection, the positivities of these cytokine mRNAs did not show a relationship with either H. pylori infection or with histological inflammation. Our findings suggest that the gastric mucosa responds to all exogenous antigens, including H. pylori, in the same fashion immunologically, and that these cytokines do not contribute to the induction of inflammation associated with H. pylori infection.
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PMID:Cytokine gene expression in the gastric mucosa: its role in chronic gastritis. 884 67

Helicobacter pylori is the major causative agent of chronic gastritis. It is associated with duodenal and gastric ulcer and with the majority of primary gastric B-cell lymphomas; furthermore, there is a strong epidemiological association with gastric cancer. One intriguing aspect of this infection is the ability of H pylori to persist despite the vast array of host immune responses. This article reviews what is known about the immune responses against H pylori, emphasizing what is generally accepted and applicable while highlighting areas of controversy. The first section delineates the genesis of the inflammatory responses, which initiate with the production of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-6, and IL-8 and continue with the recruitment of neutrophilic polymorphonuclear cells, lymphocytes, plasma cells, macrophages and eosinophils, and later with the development and recruitment of specifically committed cells (lymphocytes sensitized to H pylori antigens and B cells producing immunoglobulin (Ig)A, IgG, and possibly IgE antibodies against a variety of H pylori surface and flagellar proteins as well as bacterial toxins). The second part of the article focuses on the development of lymphoid follicles in the gastric mucosa, a phenomenon that for the first time links an immune response (the recruitment of mucosa-associated lymphoid tissue [MALT] to the gastric mucosa in response to H pylori infection) with the development of a neoplastic growth (the development of gastric MALT lymphomas). The local and systemic antibody responses are discussed in the light of their potential application in the development of diagnostic tests and vaccines. Particular emphasis is placed on the controversies surrounding the significance of antibodies directed against a 120 to 140 kDa protein apparently associated with more "aggressive" (sometimes also called "ulcerogenic" or "pathogenic") strains of H pylori.
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PMID:The immunobiology of Helicobacter pylori gastritis. 900 Apr 97

Helicobacter pylori has been shown to possess a very heterogeneous genoma despite its common phenotypic properties. Some characteristics relevant to pathogenesis have also been found to be heterogeneous. This is the case for adherence properties and the amount of urease produced, but it was not possible to relate these properties to disease entities. A vacuolating cytotoxin which alters epithelial cells has been found in about 60% of strains isolated from patients with ulcers versus 30% from those with gastritis only. The cagA gene can be used as a marker to detect the cag pathogenicity island. This DNA fragment seems to induce an increased inflammation in the gastric tissue via release of interleukin 8 by the epithelial cells. The association of this marker is strongly linked with ulcers compared with gastritis only (80% vs 55%, respectively). A number of other properties may be heterogeneous, but the low number of strains studied does not allow conclusions to be drawn.
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PMID:Pathogenic diversity of Helicobacter pylori. 908 83

Acute Helicobacter pylori infection produces predominantly neutrophilic infiltration of the gastric mucosa. However, the precise mechanisms and mediators of neutrophil migration are not known. Interleukin-8 (IL-8), a potent chemotactic factor for neutrophils, is present at high concentration in the gastric mucosa of subjects with chronic gastritis caused by H. pylori infection. The aims of this study were to determine whether IL-8 stimulates polymorphonuclear leukocyte (PMN) migration across a cultured monolayer of rabbit gastric epithelial cells and whether PMN migration affects epithelial cell barrier function. Confluent gastric epithelial monolayers grown on the inserts were overlaid with PMNs and various amounts of IL-8 were administered into the well under the insert. Gastric epithelial barrier function was assessed by sodium back diffusion. IL-8 stimulated PMN migration across the monolayer in a dose- and time-dependent manner. PMN transmigration significantly increased sodium back diffusion. In conclusion, IL-8 induces PMN migration across a monolayer of cultured gastric epithelial cells. This IL-8 action is associated with impairment of gastric epithelial barrier function. Since H. pylori infection causes a local mucosal increase of IL-8, our present findings may explain the mechanism of H. pylori-induced PMN infiltration of the gastric glands and mucosal injury.
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PMID:Interleukin-8 stimulates leukocyte migration across a monolayer of cultured rabbit gastric epithelial cells. Effect associated with the impairment of gastric epithelial barrier function. 920 Oct 86

Production of interleukin 8 (IL-8) is believed to be important in the pathogenesis of the gastritis seen in Helicobacter pylori infection. The aim of this study was to investigate the roles of protein kinase A (PKA), protein kinase C (PKC), protein tyrosine kinase (PTK) and intracellular calcium in the induction of IL-8 production by gastric epithelial cells. AGS gastric epithelial cells were stimulated with H. pylori, tumour necrosis factor alpha or interleukin 1beta together with activators or inhibitors of the relevant kinases. IL-8 production was measured by enzyme-linked immunosorbent assay. Helicobacter pylori, tumour necrosis factor alpha and interleukin 1beta produced a dose-dependent increase in IL-8 production. The increase with all three was significantly reduced by the tyrosine kinase inhibitors herbimycin A and genistein. Activation of PKC by phorbol myristate acetate was also an effective stimulus to IL-8 production and this was blocked by PKC depletion or inhibitors. Protein kinase C inhibition did not reduce the stimulation produced by H. pylori or the cytokines. Stimulation of PKA with forskolin or dibutyryl cyclic adenosine monophosphate or inhibition with H89 had no effect on IL-8 production. The calcium ionophore A23187 was a weak, PKC dependent, stimulant of IL-8 production. The production of IL-8 in AGS cells is stimulated via tyrosine kinase and protein kinase C dependent pathways. Stimulation by H. pylori, tumour necrosis factor alpha and interleukin 1beta requires tyrosine kinase activity.
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PMID:Stimulation of IL-8 production in human gastric epithelial cells by Helicobacter pylori, IL-1beta and TNF-alpha requires tyrosine kinase activity, but not protein kinase C. 923 14

Active Helicobacter pylori-associated gastritis is characterized by a dense mucosal infiltration with granulocytes. Since H. pylori is noninvasive, secondary signals must induce the accumulation of granulocytes. Interleukin-8 (IL-8) has been shown to play a key role in this event. Using competitive reverse transcriptase-PCR on mRNA from gastric biopsies, we could show a clear correlation between the amount of IL-8 transcripts and the activity of H. pylori gastritis. Due to the inability of the bacterium to invade host cells, the epithelial layer is a potential candidate as an IL-8 source. To study the mechanism of IL-8 induction, established gastric carcinoma epithelial cell lines (AGS and Kato III) and well-defined H. pylori strains were used in a modified in vitro system. The experimental design enabled us to prevent direct contact of bacteria with epithelial cells by use of a filter membrane which did not block secreted bacterial products crossing the membrane. The data clearly showed that the direct contact of the bacterial cell with the epithelial cell is necessary for optimal IL-8 production because not only live bacteria, but also metabolically inactive bacteria, increased IL-8 secretion. Neither purified lipopolysaccharide nor water-soluble protein fractions of H. pylori NCTC 11637 and Tx30a nor the cytotoxin of H. pylori was able to increase IL-8 production significantly by the epithelial cells used. Furthermore, preparations of total membrane and outer membrane proteins of H. pylori were not able to stimulate IL-8 release in vitro. Accumulatively, these results imply that active metabolism is not necessary for stimulation as long as there is an intact membrane aiding the presentation of a stimulating membrane complex or aggregate on the surface of the bacteria. From these results, we conclude that whole bacteria and their direct contact with epithelial cells may be critical for IL-8 induction in vivo.
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PMID:Role of adherence in interleukin-8 induction in Helicobacter pylori-associated gastritis. 928 28


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