interleukin-8 and Stomach-Ulcer

It remains controversial regarding the association between interleukin-8 (IL-8) gene -251 T/A polymorphism and peptic ulcer disease (PUD) risk. Thus, a large-scale meta-analysis evaluating the precise association between this gene variant and PUD risk is required. We searched the PubMed, Embase, Web of Science, and Google Scholar until April 25, 2012. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Stata 11.0. A total of eight studies (3105 subjects) were included in this meta-analysis. Overall, no significant association was found between IL-8 gene -251 T/A polymorphism and PUD risk (for A allele vs. T allele: OR = 1.17, 95% CI = 0.97-1.41, p = 0.094; for A/A vs. T/T: OR = 1.33, 95% CI = 0.94-1.90, p = 0.108; for A/A vs. A/T+T/T: OR = 1.22, 95% CI =0.97-1.52, p = 0.083; for A/A+A/T vs. T/T: OR = 1.26, 95% CI = 0.95-1.67, p = 0.113). However, in the subgroup analyses by ethnicity, H. pylori infection and the subtype of PUD, significant associations were found between IL-8 gene -251 T/A polymorphism and PUD risk in Asians, H. pylori+, duodenal ulcer disease (DUD) and gastric ulcer disease (GUD), respectively. In summary, the present meta-analysis suggests that IL-8 gene -251 T/A polymorphism is associated with increased PUD risk among Asians, and especially for the subgroups of H. pylori+, DUD and GUD.

Topics: Alleles; Asian People; Case-Control Studies; Databases, Bibliographic; Duodenal Ulcer; Gene Frequency; Haplotypes; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Risk; Stomach Ulcer

Topics: Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-17; Interleukin-8; Neutrophil Infiltration; Stomach Ulcer

The free radicals derived from oxygen have been implicated in damage caused to the gastroduodenal mucosa. The association between the mucosal production of reactive oxygen radicals in the gastric antrum and duodenum, Helicobacter pylori density and duodenal ulcer has been previously described. The role of interleukin IL-8 in the inflammatory process and its relationship with reactive oxygen radicals has also been investigated. These results indicate that oxygen radicals play an important role in the mechanism of ulcer aggravation induced by a variety of different factors.

Topics: Duodenal Ulcer; Duodenum; Free Radicals; Gastric Mucosa; Gastroenteritis; Helicobacter pylori; Humans; Interleukin-8; Reactive Oxygen Species; Stomach Ulcer

To review the role of interleukin (IL)-8 in the immunopathology of Helicobacter pylori-associated gastroduodenal disease.. Literature review.. In H. pylori infection, IL-8 secretion by the gastric mucosa is increased, particularly in patients with active neutrophilic gastritis. Immunoreactive IL-8 is evident in the epithelium of histologically normal gastric mucosa but epithelial IL-8 expression is increased in H. pylori-associated chronic gastritis. Gastric epithelial cell lines constitutively express IL-8 messenger (m)RNA and IL-8 message and protein secretion can be upregulated by the cytokines tumour necrosis factor-alpha, IL-1 alpha and IL-1 beta. H. pylori also directly induces epithelial IL-8 expression in a strain-specific manner. Cytotoxic strains expressing the CagA protein upregulate IL-8 mRNA and IL-8 protein secretion.. IL-8 is an important chemotactic and activating factor for neutrophils. The secretion of IL-8 by epithelial cells is probably a key factor in host defences at mucosal sites, permitting a rapid polymorph response against infectious agents. If defence mechanisms fail and chronic infection results, continued upregulation of IL-8 and neutrophil activation could lead to mucosal damage and increased free radical formation. Mucosal IL-8 production in H. pylori infection may be an important factor in the immunopathogenesis of peptic ulcer disease and also be of relevance to gastric carcinogenesis.

Topics: Duodenal Diseases; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Neutrophil Activation; Stomach Ulcer

Excessive systemic inflammatory response remains as a major problem underlying severe burns. This study aimed to assess the effect of low-dose glucocorticoid treatment in downregulating systemic inflammation in severely burned patients.. A prospective study from 2001 to 2014 at our hospital was conducted to compare the patients who received low-dose glucocorticoid during the acute phase with those who did not. Patients with burns 70% or greater of their total body surface area were included, and their plasma levels of inflammatory cytokines and clinical outcomes were compared.. A total of 69 patients were included in this study, with 31 patients receiving glucocorticoid treatment and the others not. Patient demographics including age, burn size, and incidence of inhalation injury were similar in both groups. The incidence of pulmonary infection and stress ulcer (and/or hemorrhage) was 24.2% and 3.0% in the treatment group, respectively, significantly lower than 47.8% and 19.6% of the control group (P < .05). Length of hospital stay was almost 13 days shorter in the treatment group (P < .05), whereas there was no significant difference in the overall mortality, duration of mechanical ventilation, and incidence of sepsis between the 2 groups. The enzyme-linked immunosorbent assay results confirmed that the plasma levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-8 were significantly lower in the treatment group (P < .05).. Low dose of glucocorticoid treatment during the acute phase could reduce the levels of proinflammatory cytokines in severely burned patients and subsequently decrease the incidence of pulmonary infection and stress ulcer, as well as the length of hospital stay.

Topics: Adult; Anti-Inflammatory Agents; Burns; C-Reactive Protein; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Glucocorticoids; Humans; Incidence; Inflammation; Interleukin-6; Interleukin-8; Length of Stay; Male; Middle Aged; Pneumonia; Prospective Studies; Sepsis; Stomach Ulcer; Treatment Outcome; Tumor Necrosis Factor-alpha

To study the effects of Jianpi Qingre Huayu Recipe in curing gastric ulcer and to preliminarily probe into its pathogenic mechanism.. Fifty patients with gastric ulcer of Pi -insufficiency and stasis-heat syndrome type were assigned to the treated group (30 patients) and the control group (20 patients). They were treated respectively with JQH and Ranitidine. At the same time, another group consisting of 20 healthy persons was set up for normal control. The clinical effect on gastroscopic figure and traditional Chinese medicine (TCM) syndrome were observed. Changes of T-cell subsets and interleukin-8 (IL-8) in serum as well as IL-8 in mucosa around the gastric ulcer were determined before and after treatment by flow cytometry and ELISA.. Comparison of the total effective rate on gastroscopic figure in the treated group and the control group (86.7% vs 80.0%) showed insignificant difference, but the cure rate and markedly effective rate in the former (50.0% and 20.0%) was higher than that in the latter (40.0% and 15.0%) respectively. Comparison of the total effective rate on TCM syndrome in the treated group and in the control group (96.7% vs 70.0%) showed insignificant difference, but the cure rate and markedly effective rate in the former (63.3% and 23.3%) was higher than that in the latter (50.0% and 20.0%) respectively. Serum levels of CD3+, CD4+, CD8+ got restored to normal range in the treated group after treatment but it was not so in the control group. IL-8 level in gastric mucosa was improved in both groups but the improvement in the treated group was better.. JQH could effectively treat gastric ulcer and partly reduce its recurrence through improving patients' immune function.

Topics: Adult; Anti-Ulcer Agents; Blood Cells; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Gastric Mucosa; Gastroscopy; Humans; Immune System; Interleukin-8; Male; Middle Aged; Ranitidine; Stomach Ulcer; T-Lymphocyte Subsets

Helicobacter pylori (Hp) is one of the most prevalent pathogenic microorganisms in the world, which is related to gastric ulcer.. To observe the effect of lansoprazole and omeprazole combined with antibiotics on gastric juice pH and inflammatory factors in elderly patients with Hp positive gastric ulcer.. This study was a prospective observation study.. This study was performed in Department of Gastroenterology, First Affiliated Hospital of Soochow University.. One hundred and ten elder patients with Hp positive gastric ulcer admitted to our hospital from January 2019 to May 2020.. The control group was treated with omeprazole combined with antibiotics, and the observation group was treated with lansoprazole combined with antibiotics.. The level of gastric juice pH, interleukin-1 (IL-1), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and heat shock protein-70 (HSP-70).. The changes of gastric juice pH value, IL-1, IL-8, TNF-α and HSP-70 levels before and after treatment were detected in the two groups. The total effective rate, Hp eradication rate, mature type of regenerated mucosal tissue surrounding ulcer and adverse reaction rate were statistically analyzed.. The total effective rate and Hp eradication rate in the observation group were higher than those in the control group, while the adverse reaction rate in the observation group was lower than that in the control group (P < .05). After treatment, the pH value of gastric juice and HSP-70 in the observation group were higher than those in the control group, while the IL-1, IL-8 and TNF-α were lower than those in the control group (P < .05). The mature type of regenerated mucosal tissue structure around ulcer in the observation group was better than that in the control group (P < .05).. The overall effect of lansoprazole combined with antibiotics in the treatment of Hp positive gastric ulcer in the elderly is better than that of omeprazole combined with antibiotics.

Topics: Aged; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Interleukin-1; Interleukin-8; Lansoprazole; Omeprazole; Prospective Studies; Stomach Ulcer; Tumor Necrosis Factor-alpha; Ulcer

To compare the anti-inflammatory activity of the crude Atractylodes lancea (AL) and AL processed products by stir-baking with bran in rat models of gastric ulcer, and preliminarily explore the anti-ulcer mechanisms of AL, the model of gastric ulcer was imitated by local acetic acid injection into gastric mucosa in rats by surgery according to the modified Okabe method. All rats were randomly divided into the following 10 groups： sham-operation group, model group, omeprazole group, Sanjiu Weitai granule group, crude AL low dose group, crude AL middle dose group, crude AL high dose group, processed AL low dose group, processed AL middle dose group, and processed AL high dose group. Rats were administered via intragastric (ig) two times each day, for 10 consecutive days. Blood was collected from the abdominal aorta, serum was separated, and the ulcer tissues were taken. The levels of inflammatory factors interleukin 6, 8 (IL-6, 8), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of TNF-α and IL-8 in gastric tissues were detected by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of TNF-α and IL-8 in gastric tissues were detected by immunohistochemistry. Compared with sham-operation group, the levels of TNF-α, IL-8, IL-6, PGE2 as well as the mRNA expressions and protein expressions of TNF-α, IL-8 in gastric tissues were significantly higher in model group. The above levels were reduced in different degrees in all treatment groups. Compared with the crude AL, same dose of processed AL was more effective in decreasing the levels of TNF-α, IL-8, IL-6, PGE2 in serum and gastric tissues and down-regulating the mRNA expressions of TNF-α and IL-8 in gastric tissues, with significant difference in middle dose groups and high dose groups. The results showed that AL had potent anti-inflammatory effects in rat models of gastric ulcer induced by acetic acid, and the processed AL had more obvious effect. The anti-ulcer action of AL could be attributed partly to down-regulating the levels of TNF-α, IL-8, IL-6 and PGE2.

Topics: Animals; Anti-Inflammatory Agents; Atractylodes; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Female; Gastric Mucosa; Humans; Interleukin-6; Interleukin-8; Male; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Tumor Necrosis Factor-alpha

The rhizome of Atractylodes lancea (AL, Compositae, Chinese name: Cangzhu; Japanese name: Sou-ju-tsu) has been used traditionally for the treatment of various diseases such as digestive disorders, rheumatic diseases, and influenza in China, Korea and Japan. The crude AL and AL bran-processed are both listed in the Chinese Pharmacopoeia. However, the differences between the effects of the crude and AL bran-processed on gastric ulcer were poorly understood, and the mechanisms for the treatment of gastric ulcer were not clear. This study aimed at comparing the anti-ulcer effects between the crude AL and AL processed in acetic acid induced model in rats and evaluating the mechanisms of action involved in the anti-ulcer properties of AL.. The model of gastric ulcer was imitated by acetic acid in rats, and AL was gavaged. The serum and gastric tissues were collected. The levels of epidermal growth factor (EGF), trefoil factor2 (TFF2), tumor necrosis factor-α (TNF-α), interleukin 6, 8 (IL-6, 8) and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of EGF, TFF2, TNF-α, and IL-8 in stomach were analyzed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, histopathological changes were evaluated by hematoxylin and eosin (HE) stain. The protein expressions of EGF, TFF2, TNF-α, and IL-8 were examined by immunohistochemistry in stomach.. The results demonstrated that the damage of gastric tissue was obviously alleviated and the productions of TNF-α, IL-8, IL-6, and PGE2 and the mRNA expressions of TNF-α, and IL-8 were notably inhibited. Furthermore, the productions of EGF and TFF2 and the mRNA expressions of EGF and TFF2 were significantly stimulated by both crude AL and AL processed in a dose-dependent manner. Compared with the crude AL, the processed AL was more effective.. The AL processed had more satisfactory effects in treatment of gastric-ulcer than the crude AL. The anti-ulcer effects of AL could be attributed to the anti-inflammatory properties via down-regulating TNF-α, IL-8, IL-6 and PGE2 and to the gastroprotective effects via up-regulating EGF and TFF2.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Atractylodes; Dietary Fiber; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Epidermal Growth Factor; Female; Interleukin-6; Interleukin-8; Male; Peptides; Powders; Rats; Stomach Ulcer; Trefoil Factor-2; Tumor Necrosis Factor-alpha

Although Helicobacter pylori (Hp) plays an important role in the pathogenesis of chronic gastritis and gastric ulcer, little is known about the probable mechanisms of these types of gastrointestinal damage. To determine the precise mechanisms involved in ulcer formation, immune responses in patients with gastric ulcer (GUP) caused by Hp infection (Hp(+)) were compared with those of other gastritis patients (GP). The sensitivity and proliferation of peripheral blood mononuclear cells (PBMNCs) obtained from patients were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against exposure with complex Hp crude antigen (HPCA) and mitogen (phytohemagglutinin, PHA). Production of inflammatory cytokines, including interleukin (IL)-1β and IL-8, in serum and supernatants of PBMNCs were then measured by ELISA. It was found that, after stimulation with PHA, both IL-8 and IL-1β concentrations in sera and supernatants as well as proliferation and sensitivity were statistically greater in GUP Hp(+) than GP Hp(-) . Furthermore, HPCA inhibited the proliferation of PBMNCs dose-dependently; however, it stimulated IL-8 and IL-1β production in supernatants of mononuclear cells. Therefore, the up-regulated concentrations of IL-8 and IL-1β may have been caused by increase in the size of mononuclear cell subpopulations or in their cytokine secretory activity, indicating the greatest cell responsiveness in GUP Hp(+) patients. These results suggest that tissue damage and ulcers occur in patients who produce more IL-8 and IL-1β than patients who do not develop ulcers; the former consequently have more activated immune cells at the site of infection. Therefore, both host responses and Hp virulence factors may be involved in the development of gastric ulcers.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Proliferation; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1beta; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Staining and Labeling; Stomach Ulcer; Tetrazolium Salts; Thiazoles; Young Adult

It has been reported that CagA gene positive Helicobacter pylori (CagA+ H. pylon) induces severe gastric mucosal inflammation. On the other hand, Interleukin (IL)-17 is known to stimulate IL-8 release by the gastric epithelial cells which facilitates chemotaxis of neutrophils through an IL-8-dependent mechanism. The aim of the study is to determine the role of IL-17 and IL-8 in the development of gastritis and gastric ulcer in H. pylori infected patients. Mucosal biopsy samples were obtained from the ulcer site of gastric mucosa of 28 patients with gastric ulcer (GU), 27 with gastritis and 8 controls subjects without gastritis or ulcers. Infection with H. pylori of patients and controls was assessed by a rapid urease test, histological examination and culture. Measurement of the tissue levels of IL-17 and IL-8 were assayed by ELISA. H. pylori cagA gene was assessed by polymerase chain reaction (PCR). Out of the 28 patients with GU, 18 (64.2%) patients were positive for H. pylori infection, while 13 (48.1%) patients with gastritis and none of the controls were positive for H. pylori infection The CagA gene was detected in 12 (66.6%) in H. pylori GU patients, and 7 (53.8%) H. pylori positive gastritis. IL-17 was significantly higher in GU-CagA+ve H. pylori compared to GU-CagA- H. pylori (P <0.05), while IL-8 showed no significant difference between groups. The mean levels of IL-8 in gastritis-CagA+ H. pylori) was significantly higher compared to gastritis--CagA- H. pylori- (P <0.05). IL-17 showed significant association with the number of neutrophils in both GU and gastritis (r = 0.689, P < 0.05 & r = 0.618, P < 0.05). Also, IL-8 showed significant association with the number of neutrophils in both GU and gastritis n (r = 0.468, P < 0.05 & r = 0.727, P < 0.05). It is concluded that the Cag+ve H. pylori is associated with induction of mucosal injury. Also, IL-8 and IL-17 plays a role in the development of GU and gastritis especially in CagA+ H. pylori.

Topics: Antigens, Bacterial; Bacterial Proteins; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-7; Interleukin-8; Polymerase Chain Reaction; Stomach Ulcer

Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degradation of extracellular matrix (ECM) and key player in various inflammatory diseases. We investigated the regulation of MMPs in chronic gastric ulceration in mice. We generated chronic gastric ulcers in mice by indomethacin and examined the activity and expression of MMP-9 and -3 in stomach. Melatonin (N-acetyl-5-methoxytryptamine) treatment has also been applied to mice to characterize the changes in expression and activities of MMPs in gastric tissues. We observed significant upregulation of MMP-9 and -3 expressions and activities in stomach with increasing doses and duration of indomethacin that corroborated with increased activity of activator protein (AP)-1. Substantial damage in gastric epithelial layer was found during chronic ulceration. Melatonin suppressed MMP-9 and -3 expressions and activities during prevention and healing of chronic gastric ulcers. It also suppressed protein oxidation, lipid peroxidation and antioxidant enzymes. Additionally, expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-8 was significantly high in ulcerated stomachs while melatonin treatment blocked them to control level. We found elevated phosphorylation of extracellular-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) during chronic gastric ulceration, which were significantly reversed by melatonin. Moreover, expression of NF-κB, c-fos and c-jun were inhibited by melatonin resulting down regulation of MMP-9 and -3 expressions. In summary, oxidative stress is preceded by chronic inflammation that enhances the expression of MMP-9 and -3, while melatonin arrests both of them via reduction of AP-1 activity during protection of ulcer.

Topics: Animals; Antioxidants; Blotting, Western; Chronic Disease; Extracellular Signal-Regulated MAP Kinases; Gastric Mucosa; Indomethacin; Interleukin-1beta; Interleukin-8; JNK Mitogen-Activated Protein Kinases; Lipid Peroxidation; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Melatonin; Mice; Mice, Inbred BALB C; NF-kappa B; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Reverse Transcriptase Polymerase Chain Reaction; Stomach; Stomach Ulcer; Transcription Factor AP-1; Tumor Necrosis Factor-alpha

TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 micg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.

Topics: Animals; Cell Adhesion; Cell Extracts; Chemokine CCL2; Coculture Techniques; Colon; Grifola; HT29 Cells; Humans; Inflammatory Bowel Diseases; Interleukin-8; Intestinal Mucosa; Monocytes; NF-kappa B; Peroxidase; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Stomach Ulcer; Transcription, Genetic; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha; U937 Cells; Weight Loss

gamma-Glutamyl transpeptidase (GGT) has been reported to be a virulence factor of Helicobacter pylori associated with bacterial colonization and cell apoptosis. But its mechanism of pathogenesis is not firmly established. This study aims to examine its role in H pylori-mediated infection.. Various H pylori isogenic mutants were constructed by a polymerase chain reaction (PCR) approach. H pylori native GGT protein (HP-nGGT) was purified with ion-exchange and gel-filtration chromatography. Generation of H2O2 was measured with fluorimetric analysis, whereas nuclear factor-kappaB (NF-kappaB) activation was determined by luciferase assay and Western blot. Cytokine production was examined by enzyme-linked immunoabsorbent assay and real-time PCR. DNA damage was assessed with comet assay and flow cytometry. The GGT activity of 98 H pylori isolates was analyzed by an enzymatic assay.. Purified HP-nGGT generated H2O2 in primary gastric epithelial cells and AGS gastric cancer cells, resulting in the activation of NF-kappaB and up-regulation of interleukin-8 (IL-8) production. In addition, HP-nGGT caused an increase in the level of 8-OH-dG, indicative of oxidative DNA damage. In contrast, Deltaggt showed significantly reduced levels of H2O2 generation, IL-8 production, and DNA damage in cells compared with the wild type (P<.05). The clinical importance of GGT was indicated by significantly higher (P<.001) activity in H pylori isolates obtained from patients with peptic ulcer disease (n=54) than isolates from patients with nonulcer dyspepsia (n=44).. Our findings provide evidence that GGT is a pathogenic factor associated with H pylori-induced peptic ulcer disease.

Topics: Apoptosis; Bacterial Proteins; Biopsy; Blotting, Western; Cells, Cultured; Chromatography, Gel; Chromatography, Ion Exchange; Comet Assay; DNA Damage; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Fluorometry; gamma-Glutamyltransferase; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen Peroxide; Interleukin-8; Mutation; NF-kappa B; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; Stomach Ulcer; Time Factors; Virulence Factors

Previous studies imply that IL-1 and IL-8 gene variations may play a crucial role in the genetic predisposition to different gastric disorders upon H. pylori infection.. The aim of this study was to determine the potential association between the prevalence of certain polymorphic sites and the risk of gastric disorders in Iranian population.. One hundred and forty three unrelated individuals with different gastric disorders and 374 normal individuals with no gastric disorders and with a negative serology test for H. pylori (control group) were studied for the association between IL-1ß (+3953 C/T) and IL-8 (-251 A/T) gene polymorphisms and H. pylori-mediated gastritis and gastric ulcer. An analysis of genotype frequency for these genes was performed using RFLP-PCR.. Based on the data obtained from culture and pathologic findings, the patients were classified into three subpopulations: H. pylori(+) non-ulcerative gastritis(+), H. pylori(+) ulcerative gastritis(+) and H. pylori(-) non-ulcerative gastritis(+). A significantly higher frequency of TT genotype (p=0.02) in IL-1ß +3953 in H. pylori(+) ulcerative gastritis(+) was revealed compared to the control group. There were no significant differences among other subpopulations. No significant differences in allele and genotype frequencies of IL-8 (-251A/T) were found among the patients.. The data suggest that TT genotype in IL-1ß +3953 may be a major contributing genetic risk factor for H. pylori induced gastric ulcer. Moreover, the role of other bacterial and host response factors, such as bacterial adherence peptides, host chemokines, and genes involved in gastric acid secretion, must be further investigated in different ethnic populations.

Topics: DNA Mutational Analysis; Gastritis; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1beta; Interleukin-8; Polymorphism, Genetic; Stomach Ulcer

Matrix metalloproteinases (MMPs) are endopeptidases which perform important functions in extracellular matrix remodeling, cell proliferation, and inflammatory processes. Here, we compared MMP-3 levels with those of tissue inhibitor of metalloproteinases (TIMP)-1 and several inflammatory cytokines in gastric ulcer (GU) patients.. This study enrolled 50 patients with GU and 6 with functional dyspepsia (FD). Samples of gastric mucosa from the antrum and the ulcer site were harvested from GU patients and of antral mucosa alone from FD patients during upper gastrointestinal endoscopy. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-3, TIMP-1, IL-1beta, IL-6, and IL-8.. All GU patients were positive for Helicobacter pylori, while all FD patients were negative. Antral levels of TIMP-1, IL-1beta, IL-6, and IL-8 were significantly higher in GU than FD patients. Further, MMP-3 levels were significantly higher in GU patients at the ulcer site than in the antrum, and had a significantly positive correlation with TIMP-1, IL-1beta, IL-6, and IL-8.. MMP-3 levels were significantly higher at the ulcer site than in the antrum, suggesting that MMP-3 may perform an important function in gastric ulcer healing.

Topics: Adult; Aged; Aged, 80 and over; Dyspepsia; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Linear Models; Male; Matrix Metalloproteinase 3; Middle Aged; Statistics, Nonparametric; Stomach Ulcer; Tissue Inhibitor of Metalloproteinase-1; Wound Healing

Zn(II)-curcumin, a mononuclear (1:1) zinc complex of curcumin was synthesized and examined for its antiulcer activities against pylorus-ligature-induced gastric ulcer in rats. The structure of Zn(II)-curcumin was identified by elemental analysis, NMR and TG-DTA analysis. It was found that a zinc atom was coordinated through the keto-enol group of curcumin along with one acetate group and one water molecule. Zn(II)-curcumin (12, 24 and 48 mg/kg) dose-dependently blocked gastric lesions, significantly reduced gastric volume, free acidity, total acidity and pepsin, compared with control group (P<0.001) and curcumin alone (24 mg/kg, P<0.05). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that Zn(II)-curcumin markedly inhibited the induction of nuclear factor-kappa B (NF-kappaB), transforming growth factor beta(1) (TGF-beta(1)) and interleukin-8 (IL-8), compared with control group (P<0.05). These findings suggested that Zn(II)-curcumin prevented pylorus-ligation-induced lesions in rat by inhibiting NF-kappaB activation and the subsequent production of proinflammatory cytokines, indicating a synergistic effect between curcumin and zinc. An acute toxicity study showed that mice treated with SDs of Zn(II)-curcumin (2 g/kg) manifested no abnormal signs.

Topics: Animals; Anti-Ulcer Agents; Base Sequence; Curcumin; DNA Primers; Dose-Response Relationship, Drug; Interleukin-8; Magnetic Resonance Spectroscopy; Male; Mice; NF-kappa B; Organometallic Compounds; Pyloric Antrum; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Stomach Ulcer; Transforming Growth Factor beta

To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats.. Gastric mucosal injury was induced in male Hos:Donryu rats by oral administration of indomethacin at a dose of 48 mg/kg. One hour before indomethacin treatment, animals were orally pretreated with irsogladine maleate at doses of 1 mg/kg, 3 mg/kg or 10 mg/kg. Four hours after indomethacin administration, the animals were sacrificed and their stomachs were rapidly removed and processed for the evaluation of gastric mucosal damage and the determination of the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-8 and myeloperoxidase (MPO) in mucosal tissues.. Linear hemorrhagic mucosal lesions were observed primarily in the glandular stomach 4 h after oral administration of indomethacin. Pretreatment with irsogladine maleate markedly reduced the number and severity of these lesions in a dose-dependent manner. The mucosal concentrations of proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-8) and MPO, which indicates the degree of mucosal infiltration by neutrophils, increased concomitantly with the occurrence of gastric injury in the indomethacin-treated rats. Pretreatment with irsogladine maleate significantly decreased the levels of these inflammatory factors in gastric tissue elicited by indomethacin.. The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction.

Topics: Animals; Anti-Ulcer Agents; Cyclic Nucleotide Phosphodiesterases, Type 4; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Gastric Mucosa; Indomethacin; Interleukin-1beta; Interleukin-8; Male; Peroxidase; Phosphodiesterase 4 Inhibitors; Phosphodiesterase Inhibitors; Rats; Stomach Ulcer; Time Factors; Triazines; Tumor Necrosis Factor-alpha

To analyze the status of expression of inflammation markers, antioxidant and oxidant enzymes in biopsies from patients diagnosed with gastritis, gastric ulcer (GU) and gastric cancer (GC) and the Helicobacter pylori virulence from these isolated biopsies in order to evaluate a possible association among these factors.. H. pylori genotype from isolated biopsies was performed by PCR. The pattern of expression of inflammation (TNF-alpha, IL-1beta, IL-8, IL-10 and IL-12), oxidant (iNOS and Nox1) and antioxidant markers (MnSOD, GPX and CAT) of biopsies from gastritis, GU, GC and control groups was performed by RT-PCR.. Different from other gastric diseases studied here, gastritis is characterized by an oxidative stress with significant expression of TNF-alpha, IL-8, IL-12, iNOS and Nox and significant absence of MnSOD and GPX expression. Gastritis was the only condition where there was an association between TNF-alpha or IL-8 expression and H. pylori cagA+/vacAs1 genotype. In this case, TNF-alpha expression was about 3 times higher when compared to control subjects.. In this study, only gastritis was found to be associated with significant oxidative stress marker expression of TNF-alpha and IL-8 that was also related to H. pylori virulence, suggesting that they are the main oxidant stress markers responsible to trigger an increase in ROS level that contributes to decrease the expression of the MnSOD and GPX.

Topics: Antioxidants; Gastritis; Gene Expression; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-10; Interleukin-12; Interleukin-8; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Nitric Oxide Synthase Type II; Oxidative Stress; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer; Tumor Necrosis Factor-alpha; Virulence

Triggering receptor expressed on myeloid cells (TREM-1) is a promoter of cytokine production triggered by microbial components. To investigate the significance of its soluble counterpart, sTREM-1, for the pathogenesis of peptic ulcer disease, sTREM-1 was compared with the proinflammatory mediators and the pathology score of gastritis.. Forty patients with dyspepsia were enrolled: 20 with peptic ulcer and 20 controls without any macroscopic abnormalities. All patients were examined by endoscopy; gastric juice was aspirated and biopsy specimens were collected from the antrum and corpus of the stomach. sTREM-1 was estimated by a hand-made enzyme immunoassay. Interleukin-8 was estimated by enzyme-linked immunosorbent assay and lipid peroxidation, indexed by malondialdehyde, by the thiobarbituric assay, after passage through a high-performance liquid chromatography system.. The median (+/-SE) of sTREM-1 of controls and patients with ulcer was 3.91+/-0.57 and 44.27+/-241.55 RU, respectively (P=0.006). The median (+/-SE) of interleukin-8 of controls and patients with ulcer was 1802.97+/-122.10 and 2030.66+/-64.44 pg/ml, respectively (P=0.023). sTREM-1 was positively correlated with the density of neutrophil and mononuclear infiltration scores and the total Sydney score (P=0.029, 0.043 and 0.041, respectively). sTREM-1 was positively correlated with interleukin-8 (P=0.042).. sTREM-1 might be an independent factor involving with the peptic ulcerative inflammatory process that is positively correlated with histopathological abnormalities of gastritis.

Topics: Cytokines; Duodenal Ulcer; Female; Humans; Interleukin-8; Intestinal Mucosa; Lipid Peroxidation; Male; Malondialdehyde; Membrane Glycoproteins; Middle Aged; Myeloid Cells; Receptors, Immunologic; Statistics, Nonparametric; Stomach Ulcer; Triggering Receptor Expressed on Myeloid Cells-1

Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process.. We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription.. The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis.. We identified the IL-8 -251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay.. IL-8 -251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 -251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in -251A carriers than in T/T carriers. In the in vitro assay, IL-8 -251A showed enhanced promoter activity in response to IL-1beta or tumour necrosis factor alpha.. The IL-8 -251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asian People; Duodenal Ulcer; Female; Gastritis; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Middle Aged; Polymorphism, Genetic; Promoter Regions, Genetic; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer

To determine the role of interleukin (IL)-17 in gastric ulcerogenesis.. Thirty-six gastric ulcer (GU) patients and 29 non-ulcer (NU) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used in in situ stimulation for 48 h in the presence of 10 microg/mL phytohemagglutinin-P (PHA), histological examination, and Helicobacter pylori (H pylori) culture. IL-17 and IL-8 protein levels in culture supernatants were assayed by ELISA. IL-17 mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). H pylori cagA and vacA status was assessed by reverse hybridization using a line probe assay (LiPA). IL-8 levels in culture supernatants were assayed after AGS cells were co-cultured with H pylori strain 26,695 or recombinant human (rh) IL-17.. All 36 GU patients and 15 of 29 NU patients were found to be H pylori-positive, while 14 NU patients were H pylori-negative. All 51 H pylori strains from both GU and NU patients were cagA- and vacAs1/m1-positive. Antral mucosal tissues from H pylori-positive patients contained significantly (H pylori-positive NU patients: median 467 pg/mg/protein, range 53-2,499; H pylori-negative NU patients: median 104 pg/mg/protein, range 16-312, P< 0.0005) higher levels of IL-17 than those from uninfected patients. IL-17 levels at the ulcer site were significantly (ulcer site: median 1,356 pg/mg/protein, range 121-1,3730; antrum: median 761 pg/mg/protein, range 24-7,620, P< 0.005) higher than those at distant sites in the antrum. Biopsies from H pylori-positive GU and NU patients showed IL-17 mRNA expression in all samples whereas those from the antrum of the H pylori-negative controls showed no detectable expression. A significant correlation was seen between IL-17 and IL-8 levels at each biopsy site (ulcer: r = 0.62, P< 0.0001; antrum: r = 0.61, P< 0.0001) in GU patients. RhIL-17 and H pylori strain 26,695 each stimulated IL-8 production from AGS cells.. IL-17 may play an important role in the inflammatory response to H pylori colonization, and may ultimately influence the outcome of H pylori-associated diseases that arise within the context of gastritis.

Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Biopsy; Epithelial Cells; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-17; Interleukin-8; RNA, Messenger; Stomach Ulcer

To assess the synergistic action of famotidine (FMD) and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats.. Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n = 8), control group (n = 8), FMD group (n = 8), CPA group (n = 8), and FMD+CPA group (n = 8). Each group was given intraperitoneally (i.p.) 0.5 mL/100 g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10 mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively, daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenization was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF(1a)) and IL-8 were determined by radioimmunoassay.. The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGF(1a) and MPO were confirmed. The effect of FMD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm(2)) was reduced from 40.18+/-2.6 in control group to 6.83+/-2.97 in PMD+CPA group, P<0.01, and from 32.9+/-3.27 in FMD group to 6.83+/-2.97 in PMD+CPA group, P<0.01. The plasma levels of IL-8 decreased from 0.69+/-0.11 ng/L in control group to 0.4+/-0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51+/-0.08 ng/L in FMD group to 0.4+/-0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGF(1a) increased from 7.55+/-1.65 ng/L in control group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.01, and from 13.15+/-1.48 ng/L in FMD group to 16.62+/-0.97 ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12+/-2.05 u/L in control group to 4.33+/-0.95 u/L in PMD+CPA group, P<0.01, and from 8.3+/-1.29 u/L in FMD group to 4.33+/-0.95 u/L, P<0.01.. The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the healing of ulcer.

Topics: 6-Ketoprostaglandin F1 alpha; Acetic Acid; Animals; Chlorpheniramine; Chronic Disease; Drug Synergism; Famotidine; Histamine H1 Antagonists; Histamine H2 Antagonists; Interleukin-8; Liver; Male; Peroxidase; Rats; Rats, Sprague-Dawley; Stomach Ulcer

Topics: Apoptosis; DNA; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interferon-gamma; Interleukin-6; Interleukin-8; RNA, Messenger; Stomach Ulcer; Tumor Necrosis Factor-alpha

Oxygen radicals are important regulators in Helicobacter pylori-induced gastric ulceration and carcinogenesis. IL-8 may be regulated by oxidant-sensitive transcription factors, NF-kappaB, and AP-1. The present study aims to investigate whether H. pylori-induced IL-8 expression is regulated by NF-kappaB and AP-1 in gastric epithelial AGS cells and whether this transcriptional regulation of IL-8 is inhibited by N-acetylcysteine (NAC). As a result, H. pylori induced the expression of mRNA and protein for IL-8 via activation of NF-kappaB and AP-1. NF-kappaB activation accompanied by a decrease in I-kappaBalpha and activated AP-1 complex was a c-jun/c-fos heterodimer in H. pylori-infected AGS cells. NAC inhibited H. pylori-induced activation of transcription factors and IL-8 expression in AGS cells. In conclusion, oxygen radicals induce the activation of NF-kappaB and AP-1 and IL-8 expression. Antioxidants such as NAC might be useful anti-inflammatory agents by inhibiting activation of transcription factors and decreasing IL-8 production in H. pylori-induced gastric inflammation.

Topics: Analysis of Variance; Base Sequence; Blotting, Northern; Blotting, Western; Cells, Cultured; Epithelial Cells; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Molecular Sequence Data; NF-kappa B; Polymerase Chain Reaction; Probability; Reactive Oxygen Species; RNA, Messenger; Sensitivity and Specificity; Stomach Ulcer; Transcription Factor AP-1

NSAID use and Helicobacter pylori both cause damage to the gastric mucosa and can cause peptic ulcers. Our aim was to test the relationship between gastric mucosal polymorphonuclear leukocyte (PMN) infiltration and the severity of NSAID-induced gastric injury. H. pylori density, mucosal interleukin-8 (IL-8), and nitrite levels were assessed after receiving placebo and again after receiving 1000 mg of naproxen daily for three days. Histology was graded using a visual analog scale (0-5). IL-8 levels were assayed by ELISA and nitrite levels by Griess reaction. Eleven healthy volunteers with H. pylori infection entered. All had normal-appearing gastric mucosa after placebo. Postnaproxen gastric damage included three with none, one with mild, three with moderate, two with severe, and three were very severe mucosal injury (including one with an ulcer >5 mm). There was an inverse correlation between endoscopic score and the pH of the gastric juice post-therapy (R = -0.77, P = 0.004). There was no significant change in histologic or biochemical parameters from pretreatment levels. And none of the parameters (eg, PMN density) predicted endoscopic outcome. In conclusion, there was no relation between mucosal PMN density and endoscopic mucosa injury. PMN infiltration, while not predictive, may be a surrogate for an H. pylori infection-related increased risk of NSAID ulcers.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Cell Count; Female; Gastric Acidity Determination; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Interleukin-8; Male; Middle Aged; Naproxen; Neutrophils; Nitrites; Stomach Ulcer

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.

Topics: Animals; Antigens, Bacterial; Apoptosis; Bacterial Proteins; Cell Division; Cell Line; Duodenal Ulcer; Gastric Mucosa; Gastritis; Genome, Bacterial; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Interleukin-8; Oligonucleotide Array Sequence Analysis; Sequence Deletion; Stomach Ulcer

To investigate whether Helicobacter pylori infection, but not drugs, affects gastric somatostatin, interleukin-8 (IL-8), histological inflammation through eradication therapy, and interactions among these parameters.. Twenty-eight H. pylori-positive patients (21 males; mean age 47.0 years) with either gastric ulcer (GU: n = 11) or duodenal ulcer (n = 17) diagnosed endoscopically were treated with dual therapy. Eradication was defined as negative microbiologic tests and 13C-urea breath test. Levels of antral and gastric juice somatostatin and mucosal IL-8 were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Histology was assessed by the Sydney system.. H. pylori was eradicated in 15 patients (10 males, 6 GU) out of 28 (54%). The patients' backgrounds did not affect the eradication of H. pylori. Successes in eradication significantly increased antral and juice somatostatin contents, and dramatically decreased IL-8 levels and histological gastritis. In contrast, persistent H. pylori infection did not affect somatostatin and histological gastritis. An inverse correlation was present between changes in somatostatin levels and histological activity. No relationship was observed in changed values between antral somatostatin and IL-8.. These results indicate that eradication of H. pylori, but not the drugs used, induced an increase in somatostatin levels in the antrum and gastric juice, suggesting a close relationship between H. pylori and gastric somatostatin regulation. A close correlation between an increase in gastric somatostatin levels and the normalization of histological activity was present, suggesting that certain peptide-immune interactions in the gastric mucosa exist in H. pylori infection.

Topics: Adult; Aged; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Gastric Juice; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Intestinal Mucosa; Male; Middle Aged; Peptic Ulcer; Pyloric Antrum; Somatostatin; Stomach; Stomach Ulcer

Sofalcone has been reported to exert anti-ulcer and gastroprotective actions, but its exact mechanism of action remains unknown. In our laboratory, we found that indomethacin-induced gastric ulcers become worse when associated with Helicobacter pylori infection.. We employed the H. pylori-infected gnotobiotic murine model to examine the effect of sofalcone on indomethacin-induced gastric ulcers in the presence of H. pylori infection. In vitro experiments were also done to evaluate the effects of sofalcone on H. pylori growth, adherence of H. pylori to the MKN45 cells (a human gastric epithelial cell line), and these cells' IL-8 production in the presence of H. pylori.. We found that sofalcone produced a significant improvement in ulcer size as well as a substantial reduction in the number of H. pylori colonies in H. pylori-infected gnotobiotic mice. In vitro sofalcone has a significant bacteriocidal effect against H. pylori and can also significantly prevent adherence of this bacterium to MKN45 cells, thus remarkably reducing IL-8 production of these cells in response to stimulation by H. pylori.. Our results suggest that sofalcone can improve ulcer healing by the mechanisms mentioned above.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Cell Adhesion; Chalcone; Chalcones; Disease Models, Animal; Helicobacter Infections; Helicobacter pylori; Humans; Indomethacin; Interleukin-8; Mice; Mice, Inbred BALB C; Stomach Ulcer

It has been suggested that gastric mucosal injury induced by Helicobacter pylori infection is mediated by interleukin-8 (IL-8).. We studied the effect of plaunotol, a drug extracted from the Plau-noi tree of Thailand, and reported it to be effective in the treatment of ulcers, of IL-8 secretion induced by H. pylori and of the inhibitory adhesion activity of the bacterium to gastric epithelial cells. Moreover, the therapeutic effect of plaunotol on H. pylori infection was assessed by using the gnotobiotic murine model.. Plaunotol inhibited the growth of H. pylori (1.5 x 10(4) c.f.u./mL) at high doses (24-48 microg/mL), but not at low doses (3-6 microg/mL). Interleukin-8 secretion induced by H. pylori was inhibited by coculture with plaunotol in a dose-dependent manner. The adhesion of H. pylori to MKN45 cells was also suppressed by coculture with plaunotol in a dose-dependent manner. An in vivo study showed that plaunotol improved histological gastritis and decreased the H. pylori antibody titre.. These findings suggest that plaunotol has a therapeutic effect on gastritis induced by H. pylori.

Topics: Administration, Oral; Animals; Anti-Ulcer Agents; Antibodies, Bacterial; Bacterial Adhesion; Diterpenes; Dose-Response Relationship, Drug; Epithelial Cells; Fatty Alcohols; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Immunoassay; Interleukin-8; Male; Mice; Mice, Inbred BALB C; Rabbits; Stomach Neoplasms; Stomach Ulcer; Tumor Cells, Cultured

Although mucosal alpha- and beta-chemokines are considered to be involved in the pathogenesis of Helicobacter pylori-associated gastritis, little is known how these chemokines are related to the ulcerogenesis in peptic ulcer patients. We examined the levels of interleukin (IL)-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures and the numbers of inflammatory cells infiltrating the lamina propria by using the mucosal tissues obtained from gastric ulcer (GU) patients with and without H. pylori infection.. Levels of IL-8 and MIP-1alpha secreted in organ cultures were measured by an enzyme-linked immunosorbent assay. Numbers of myeloperoxidase-positive neutrophils, CD68-positive macrophages, and mononuclear cells were determined in tissue sections.. The mucosal tissues of both the gastric antrum and the ulcer site obtained from patients with H. pylori-positive GU showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of inflammatory cells compared with the corresponding mucosal tissues from those with H. pylori-negative GU or the antral mucosal tissues from H. pylori-negative controls. When the values were compared between the mucosal tissues from the gastric antrum and those from the ulcer site, the latter group of tissues showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of neutrophils and macrophages than the former group regardless of its healing process in patients with H. pylori-positive GU.. Mucosal alpha- and beta-chemokines may be important to the ulcerogenesis in H. pylori-associated GU disease.

Topics: Adult; Chemokine CCL3; Chemokine CCL4; Female; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Intestinal Mucosa; Macrophage Inflammatory Proteins; Male; Middle Aged; Stomach Ulcer

In Helicobacter pylori-associated gastric mucosal injury, interleukin (IL) -8, a potent leukocyte chemoattractant, is produced by epithelial cells infected by H. pylori and directs neutrophils to the gastric mucosa. According to previous studies, the IL-8 production requires direct contact between the bacteria and epithelial cells. The aims of the present study were to determine whether an H. pylori water extract (HPE) induces IL-8 production by gastric epithelial cells and to characterize IL-8-inducing substances in HPE. Extracts were prepared from a standard strain and from strains obtained from patients with gastric ulcers. After addition of HPE to MKN 45 cells, a gastric cancer cell line, IL-8 in supernatants and IL-8 mRNA were measured by immunoassay and reverse transcription-polymerase chain reaction, respectively. For characterization, active fractions obtained by gel filtration of standard-strain HPE were treated by heating or trypsinization. To study the signal pathway leading to IL-8 production, inhibitors for protein kinase A (PKA), protein kinase C (PKC), or protein tyrosine kinase (PTK) were incubated with MKN45 cells before HPE stimulation. HPE from the standard strain and one of these clinical strains induced IL-8 production. Lipopolysaccharide or cagA in the strains showed no correlation with IL-8 concentration. Standard-strain HPE induced IL-8 mRNA expression in MKN 45 cells. Gel filtration localized activity to a low-molecular-weight fraction of about 7 kDa, which was resistant to heat and trypsin digestion. PKC inhibitors significantly blocked HPE-induced IL-8 production by MKN 45 cells; however, the PKA inhibitor or PTK inhibitors showed a partial inhibitory effect. HPE contains a nonprotein substance of low molecular weight that is responsible for IL-8 induction in gastric epithelial cells. This induction is mainly dependent on the activation of PKC but partially also dependent on PKA or PTK.

Topics: Cells, Cultured; Cyclic AMP-Dependent Protein Kinases; Epithelium; Gastric Mucosa; Helicobacter pylori; Humans; Interleukin-8; Protein Kinase C; Protein-Tyrosine Kinases; RNA, Messenger; Stomach Ulcer; Tumor Cells, Cultured

Helicobacter pylori (H. pylori) appears to initiate an inflammatory cascade. Thus, phagocytes are accumulated in the gastric mucosa, in inflammatory conditions. Further, a potent chemotactic mediator, interleukin 8 (IL-8) is synthesized at such sites. The recently described IL-8 autoantibodies may, however, counteract the pro-inflammatory actions of IL-8. The aim was to study the correlation between H. pylori infection and IL-8, together with IL-8 autoantibodies in two different populations from a developed and a developing country.. Two different endoscopically characterized populations (65 Danes and 89 Albanians) were examined. IL-8 and IL-8 autoantibodies were detected by ELISA techniques, and H. pylori was identified by histological examinations.. Significantly more Albanian controls and dyspeptic patients (80 out of 89 persons) were H. pylori positive as compared to 24 of 65 Danes (p < 0.001). The median IL-8 level among Albanian controls 349 pg/mg protein was significantly higher than among Danes < 61 pg/mg protein (p < 0.001), and was at the same level as found in Danish peptic ulcer patients (p > 0.05). Further, H. pylori positive patients from both countries had significantly higher levels of IL-8 as compared to H. pylori negative patients (p < 0.001). However, significantly higher levels of IL-8 autoantibodies were found in the Albanian sub-population (median 138 O.D. units versus 52 O.D. units among Danes) (p < 0.001).. In H. pylori related disorders, a high mucosal IL-8 production has been found. However, this investigation further demonstrates higher levels of IL-8 autoantibodies among dyspeptic patients from a developing country, which might possibly counteract the pro-inflammatory actions of IL-8 by binding the molecule. The physiological significance of an altered immune response as described here needs to be elucidated in future studies.

Topics: Adolescent; Adult; Aged; Autoantibodies; Duodenal Ulcer; Duodenitis; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Middle Aged; Stomach Ulcer

It is well known that antrum-predominant gastritis and pan-gastritis occurs in the patients with Helicobacter pylori-positive duodenal ulcer (DU) and gastric ulcer (GU), respectively. However, the role of chemokines in the pathogenesis of these pathologies is unclear. We examined the regional differences in mucosal chemokine production in patients with DU and GU. The production of interleukin-8 (IL-8), growth-related gene (GRO) alpha, and macrophage inflammatory protein (MIP)-1alpha was greater in the antrum than in the corpus in DU patients. In the patients with GU, monocyte chemoattractant protein (MCP)-1 levels in the mucosa adjacent to ulcer were greater than those away for the ulcer in the corpus. The reduction in chemokine production occurring in association with the eradication of H. pylori differed between DU and GU patients in the antrum (IL-8, P = 0.0394; GROalpha, P = 0.0149; MIP-1alpha, P = 0.0246; MCP-1, P = 0.0087). The data imply a different pathogenesis may exist for the gastritis present in patients with DU and GU occurring in H. pylori-positive individuals.

Topics: Adult; Aged; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5; Chemokine CXCL1; Chemokines; Chemokines, CXC; Chemotactic Factors; Duodenal Ulcer; Female; Gastric Mucosa; Growth Substances; Helicobacter Infections; Helicobacter pylori; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Macrophage Inflammatory Proteins; Male; Middle Aged; Organ Culture Techniques; Pyloric Antrum; Stomach Ulcer

C-X-C Chemokines play an important role for neutrophil extravasation through microvessels. Although the level of interleukin (IL)-8 is known to increase in the Helicobacter pylori-infected gastric mucosa, another C-X-C chemokine, GROalpha, has not been evaluated in the H. pylori-associated gastric mucosal injury. The present study was designed to investigate gastric contents of GROalpha in relation to those of IL-8 in the gastric mucosa of H. pylori-infected peptic ulcer patients. Thirty-eight patients with gastric ulcer and 41 with gastritis underwent endoscopy with informed consent and 49 were found to be H. pylori positive and 30 H. pylori negative. Biopsies from the gastric corpus were performed in each patient to examine the H. pylori colonization by bacterial culture, the rapid urease test and histological specimens as well as measurement of the contents of human GROalpha and IL-8. Helicobacter pylori infection was eradicated in 21 patients by triple therapy (lansoprazole 30 mg, amoxycillin 2.0 g, clarithromycin 600 mg; 2 weeks). The samples for GROalpha and IL-8 assay were homogenized in 0.02% aprotinin containing phosphate-buffered solution and the mucosal contents of GROalpha and IL-8 in the supernatants were quantified by sandwich enzyme immunoassay methods. The levels of GROalpha and IL-8 in H. pylori-positive gastric mucosa were significantly higher than those in the H. pylori-negative mucosa. There was a significant linear correlation between the levels of GROalpha and IL-8 (r = 0.798, P < 0.01). After the eradication of H. pylori by the triple therapy, the levels of GROalpha and IL-8 were significantly decreased. The GROalpha showed an increase in the H. pylori-positive gastric mucosa in a similar fashion as IL-8 contents, suggesting a pathogenetic role for GROalpha in H. pylori-associated gastric mucosal injury.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Chemokine CXCL1; Chemokines, CXC; Chemotactic Factors; Gastric Mucosa; Gastritis; Growth Substances; Helicobacter Infections; Helicobacter pylori; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Lansoprazole; Middle Aged; Omeprazole; Stomach Diseases; Stomach Ulcer

It is well known that Helicobacter pylori can cause gastritis, gastroduodenal ulcers and malignant diseases. The infiltration of polymorphonuclear leukocytes is recognized in the lesions of these diseases, and the infiltration disappears by antibiotic therapy. However, it is not yet clarified how Helicobacter pylori induces the formation of lesions including leukocyte infiltration. Recently, we have confirmed that several kinds of cytokines are expressed in the gastric biopsy specimens of gastroduodenal diseases. Especially, it is conjectured that chemokines such as interleukin-8 (IL-8) which are expressed in the specimens, induce leukocyte infiltration, gastric mucosal inflammation and gastroduodenal ulcers. It is possible that Helicobacter pylori CagA gene is closely related with IL-8 expression because this cytokine is more strongly expressed in the specimens from the patients infected with CagA-positive Helicobacter than those with CagA-negative one.

Topics: Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Proteins; Cytokines; Duodenal Ulcer; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Stomach Ulcer

We examined the relationship between the levels of macrophage inflammatory protein 1alpha (MIP-1alpha) and interleukin-8 (IL-8) in organ cultures of antral mucosal tissues, background gastroduodenal diseases, and grades of histologic gastritis. Significantly higher levels of MIP-1alpha and IL-8 were detected in patients with H. pylori infection than in those without infection. In H. pylori-positive patients, mucosal specimens from patients with peptic ulcer disease showed higher levels of MIP-1alpha and IL-8 than the specimens obtained from patients with erosive gastritis or those from endoscopically normal mucosa, and this was particularly pronounced in patients with duodenal ulcer. There were positive correlations between MIP-1alpha and IL-8 levels and histologic grades of activity, inflammation, and H. pylori density as defined by the Sydney system. However, the degree of association with the inflammatory cell count was different between these two chemokines. MIP-1alpha levels had a stronger association with mononuclear cells than with neutrophils, whereas IL-8 levels showed an association with neutrophils and mononuclear cells to an almost equal degree. These results suggest that MIP-1alpha and IL-8 may play important roles as inflammatory mediators in the pathogenesis of histologically proven H. pylori-associated gastritis.

Topics: Adult; Case-Control Studies; Chemokine CCL3; Chemokine CCL4; Culture Techniques; Duodenal Ulcer; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Macrophage Inflammatory Proteins; Male; Middle Aged; Pyloric Antrum; Stomach Ulcer

To appraise the effect of certain pro-inflammatory mediators on the pathogenesis of acute gastric mucosal lesion in early burn stage.. 21 patients with burn injuries of over 30% TBSA were divided into A and B groups according to the main clinical indexes during shock resuscitation and hemodynamic parameters. Fiberoptic endoscopic examination, determination of intramucosal pH (pHi) and measurement of some mediators were done immediately after admission to the hospital and 4 and 7 days after burn injury.. It was demonstrated that the level of LPS in plasma, the content of TNF-alpha, IL-8 and ET in group B at 4 and 7 days postburn were significantly higher than those of group A, while the value of pHi in group B was markedly lower than that of group A. Damaging index of gastric mucosa was negatively correlated with pHi (r = -0.89, P < 0.05), but positively with ET (r = 0.91, P = 0.05).. These findings suggest that the inflammatory mediators and cytokines promoted secondary damage to gastric mucosa during early postburn. It was believed that pHi was a sensitive index, and it played an important role in the development of stress ulceration.

Topics: Adolescent; Adult; Burns; Endothelins; Female; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Interleukin-8; Male; Middle Aged; Stomach Ulcer; Tumor Necrosis Factor-alpha

To determine the mechanisms of gastric mucosal injury associated with Helicobacter pylori infection, we investigated the contents of cytokines and inflammatory cell infiltration in the gastric mucosa. Ninety-six patients with dyspepsia were studied (58 gastric ulcer, 38 nonulcer dyspepsia). Of the 96 patients, 63 were infected with H. pylori as determined by microscopic examination with HE staining, culture of H. pylori, or the rapid urease test. Endoscopic biopsy specimens were obtained from both the antrum and the body to examine interleukin (IL)-8, IL-6, IL-1 beta, and tumor necrosis factor-alpha contents in the gastric mucosa by enzyme-linked immunosorbent assay. Inflammatory cell infiltration was assessed according to the Sydney system. IL-8 content was enhanced in both the antral and body mucosa of the H. pylori-positive patients compared with the H. pylori-negative patients. Furthermore, IL-8 content correlated well with the infiltration of both mononuclear cells and polymorphonuclear cells. These results suggest that IL-8 plays important roles in the pathogenesis of gastric mucosal injury associated with H. pylori infection.

Topics: Case-Control Studies; Cytokines; Dyspepsia; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Middle Aged; Stomach Ulcer

Neutrophil accumulation plays an important role in Helicobacter pylori-associated gastric mucosal injury. In this study, the mucosal content of myeloperoxidase (MPO), which is a measure of neutrophil accumulation and interleukin-8 (IL-8) was assayed and changes in MPO and IL-8 content were determined before and after H. pylori eradication therapy. Thirty-seven H. pylori-positive patients (11DU/26GU) underwent H. pylori eradication therapy with lansoprazole (30 mg/day, 6 weeks) and amoxicillin (2 g/day, 2 weeks), followed by famotidine (20 mg/day, 8 weeks). H. pylori-infection status was evaluated by routine endoscopic examinations (culture, CLO, histology). Immediately and 8 weeks after cessation of the anti-H. pylori therapy, these tests were repeated. Intragastric urease activity was estimated by delta 13CO2, which was obtained by the [13C]urea breath test (UBT). Mucosal samples were taken and tissue MPO and IL-8 contents were assayed by EIA and ELISA, respectively. Histologic examination was also performed. Among the 37 patients, 21 cases of H. pylori infection were eradicated (56.8%). Intragastric urease activity was dramatically reduced immediately after the anti-H. pylori therapy, whereas, it was re-elevated 8 weeks later in the relapsed cases. Antral MPO content was decreased in the eradicated and relapsed cases. MPO in the corpus was also decreased in the eradicated cases. Nevertheless, it was enhanced (3.5-fold) in the relapsed cases at 8 weeks after therapy. Changes in mucosal IL-8 content were similar to those of MPO. In eradicated cases, neutrophil infiltration is improved in both the antrum and corpus. However failure of eradication therapy results in the enhancement of neutrophil accumulation in the corpus. Further study is necessary to clarify the mechanism of neutrophil accumulation after therapy for H. pylori.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Drug Therapy, Combination; Duodenal Ulcer; Famotidine; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Lansoprazole; Male; Middle Aged; Neutrophils; Omeprazole; Peroxidase; Proton Pump Inhibitors; Stomach Ulcer

Topics: Animals; Indomethacin; Interleukin-8; Male; Rats; Rats, Sprague-Dawley; Stomach Ulcer

To examine the background histology, interleukin-8 (IL-8) secretion, and expression of IL-8 mRNA and protein, using the gastric antral mucosa infected with Helicobacter pylori.. The antral biopsies were obtained from an area of endoscopically intact mucosa in 147 patients whose endoscopic diagnoses were normal (n = 41), duodenal ulcer (n = 58), gastric ulcer (n = 21), or gastritis (n = 27). Levels of IL-8 secreted in the organ cultures of mucosal biopsies were measured by an ELISA assay, and the expression of IL-8 mRNA and protein was analyzed in fresh biopsy tissues with RT-PCR and immunofluorescent microscopy, respectively.. Significantly greater levels of IL-8 were secreted in patients with H. pylori infection, and its elevation was more prominent in duodenal ulcer patients than in those with gastric ulcer or endoscopically defined gastritis. There was an association among H. pylori density, IL-8 activity, and histological severity of activity and inflammation of gastritis in the Sydney system. Consistent with enhanced IL-8 activity in the organ cultures, IL-8 mRNA was detected in 16 of 23 fresh biopsy tissues studied in H. pylori-positive patients. In contrast, IL-8 transcript was detected in only one of 12 H. pylori-negative cases. Immunofluorescent microscopy showed localization of IL-8 protein in the gastric epithelial cells and lamina propria cells, primarily CD68+ macrophages in specimens with H. pylori infection.. This study indicates that a strong correlation exists between mucosal IL-8 activity and histological severity in H. pylori-associated antral gastritis. Further studies will be necessary to determine the mechanisms involved in elevated mucosal IL-8 activity in H. pylori infection.

Topics: Adult; Biopsy; Duodenal Ulcer; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; Organ Culture Techniques; Pyloric Antrum; RNA, Messenger; Stomach Ulcer

To evaluate the inflammatory changes during ulcer healing, we measured myeloperoxidase (MPO) activity and the inflammatory cytokine interleukin-8 (IL-8) in the gastric mucosa of 51 patients with gastric ulcers and 5 normal controls. MPO activity was measured by enzyme assay and IL-8 by ELISA, using biopsy samples taken from the ulcer margin and at 3 and 6 cm from the ulcer. Levels of MPO activity were significantly higher than in normal controls and peaked at the A2 (active) stage, and then gradually decreased and returned to basal levels at the S2 (scarring) stage. The area of increased MPO activity around the gastric ulcer was approximately 6 cm in diameter at the A2 stage, and this area decreased as the ulcer healed. IL-8 levels in gastric mucosa also increased significantly at the A2 stage, and the changes paralleled those of MPO activity during ulcer healing. MPO activity correlated well with the IL-8 level.

Topics: Biopsy; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Interleukin-8; Peroxidase; Stomach Ulcer