interleukin-8 and Esophagitis--Peptic

Recent reports have demonstrated significantly higher expression levels of interleukin-8 (IL-8) in patients with gastroesophageal reflux disease (GERD) including non-erosive reflux disease (NERD). The levels of IL-8 mRNA expression were significantly decreased after proton pump inhibitor. The esophageal expression of CINCs, rat IL-8-like chemokines, was markedly enhanced in the models of acute or chronic esophagitis in rats. The production of IL-8 from esophageal mucosal cells was enhanced by the exposure to bile acid. These results suggest that IL-8 chemokine may play a major role in the pathogenesis of esophageal inflammation in GERD.

Topics: Animals; Barrett Esophagus; Bile Acids and Salts; Chemokines, CXC; Depression, Chemical; Disease Models, Animal; Enzyme Inhibitors; Esophagitis, Peptic; Esophagus; Gastroesophageal Reflux; Gene Expression; Humans; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Interleukin-8; Mucous Membrane; Proton Pump Inhibitors; Rats; RNA, Messenger

To explore the protective effects and therapeutic mechanism of Esomeprazole (PPI), polaprezinc granule (PZ), and PPI + PZ on reflux esophagitis (RE) in the rat model.. Wistar rats were randomly divided into 9 groups, which contain the control group, the acid cessation group (0.7% HCl, Q3D × 4), and the acid persistence group (0.7% HCl, Q3D × 11). PPI was administered by gavage at 8 mg·kg. The ELISA results showed that the levels of IL-8 and PGE2 were significantly increased in the model group, but decreased in all groups after treatment. In the acid cessation group, PZ treatment had the most significant effect on reducing IL-8 levels and PPI + PZ treatment had the most significant effect on reducing PGE2 levels. In the acid persistence group, the PPI treatment had the most significant effect on reducing the levels of IL-8 and PGE2, and the PZ treatment could also significantly reduce their levels, close to the normal value. Western blot results showed that the expression of PI3K/Akt/mTOR pathway protein was increased in the model group, while its expression was decreased after treatment.. Polaprezinc has a significant therapeutic effect on RE in rats, which can reduce the levels of IL-8 and PGE2 and downregulate the expression of PI3K/Akt/mTOR signal pathway protein. The efficacy of polaprezinc in the treatment of reflux esophagitis is comparable to that of PPI, and the combination of them is more effective in the reflux esophagitis treatment.

Topics: Animals; Dinoprostone; Esophagitis, Peptic; Interleukin-8; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; TOR Serine-Threonine Kinases

To investigate the effect of dietary ratio of n-6/n-3 PUFAs on chronic reflux esophagitis (RE) and lipid peroxidation.. Rat RE model were established and then fed on a diet contained different n-6/n-3 PUFA ratios (1:1.5, 5:1, 10:1) or received pure n-6 PUFA diet for 14 days. Esophageal pathological changes were evaluated using macroscopic examination and hematoxyline-eosin staining. IL-1β, IL-8, and TNFα mRNA and protein levels of were determined using RT-PCR and Western blotting, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using ELISA.. The severity of esophagitis was lowest in the PUFA(1:1.5) group (P<0.05). IL-1β, IL-8, and TNFα mRNA and protein and MDA levels were significantly increased in model groups with the increasing n-6/n-3 PUFA ratios. SOD levels were significantly decreased in all RE PUFA groups (P<0.05).. Esophageal injury and lipid peroxidation appeared to be ameliorated by increased n-3 PUFAs intake.

Topics: Animals; Anti-Inflammatory Agents; Dietary Fats; Disease Models, Animal; Esophagitis, Peptic; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Gene Expression Regulation; Humans; Interleukin-1beta; Interleukin-8; Lipid Peroxidation; Male; Malondialdehyde; Rats; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Polyunsaturated fatty acids (PUFAs) play various roles in inflammation. However, the effect of PUFAs in the development of reflux esophagitis (RE) is unclear. This study is to investigate the potential effect of n-3/n-6 PUFAs on acute RE in rats along with the underlying protective mechanisms.. Forty Sprague Dawley rats were randomly divided into four groups (n = 10 in each group). RE model was established by pyloric clip and section ligation. Fish oil- and soybean oil-based fatty emulsion (n-3 and n-6 groups), or normal saline (control and sham operation groups) was injected intraperitoneally 2 h prior to surgery and 24 h postoperatively (2 mL/kg, respectively). The expressions of interleukin (IL)-1β, IL-8, IL-6 and myeloid differentiation primary response gene 88 (MyD88) in esophageal tissues were evaluated by Western blot and immunohistochemistry after 72 h. The malondialdehyde (MDA) and superoxide dismutase (SOD) expression in the esophageal tissues were determined to assess the oxidative stress.. The mildest macroscopic/microscopic esophagitis was found in the n-3 group (P < 0.05). The expression of IL-1β, IL-8, IL-6 and MyD88 were increased in all RE groups, while the lowest and highest expression were found in n-3 and n-6 group, respectively (P < 0.05). The MDA levels were increased in all groups (P < 0.05), in an ascending trend from n-3, n-6 groups to control group. The lowest and highest SOD levels were found in the control and n-3 group, respectively (P < 0.05).. n-3 PUFAs may reduce acute RE in rats, which may be due to inhibition of the MyD88-NF-kB pathway and limit oxidative damage.

Topics: Animals; Disease Models, Animal; Esophagitis, Peptic; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fish Oils; Gene Expression Regulation; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Malondialdehyde; Myeloid Differentiation Factor 88; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxide Dismutase-1

To observe the effects of quercetin on chronic mixed reflux esophagitis (RE) in rats by inhibiting the nuclear factor-κB p65 (NF-κBp65) and interleukin-8 (IL-8) signaling pathways.. Forty-eight healthy male Sprague-Dawley rats were randomly divided into six groups, with 8 rats in each group: the normal intact group, the sham operation group, the RE control group, the RE group treated with omeprazole or 100 mg/kg and 200 mg/kg quercetin. The animals were sacrificed after 6 weeks of different interventions. The pathological characteristics of esophageal mucosa were observed according to the diagnostic criteria and the expressions of NF-κBp65 and IL-8 were assessed by immunohistochemistry and real-time polymerase chain reaction.. Compared with the RE control group, esophageal mucosal injury was improved and the expressions of NF-κBp65 and IL-8 were significantly decreased in the RE group treated with omeprazole or quercetin (P < 0.05). Compared with the omeprazole group, the gross and microscopic scores of esophageal mucosal injury and the expressions of NF-κBp65 and IL-8 in the 100 mg/kg and 200 mg/kg quercetin groups were not increased (P > 0.05). There was no statistically significant difference between the RE groups treated with 100 mg/kg quercetin and 200 mg/kg quercetin.. Quercetin can prevent esophageal mucosal injury in RE rats by suppressing the NF-κBp65 and IL- 8 signaling pathways.

Topics: Animals; Antioxidants; Drug Evaluation, Preclinical; Esophagitis, Peptic; Interleukin-8; Male; Quercetin; Rats; Rats, Sprague-Dawley; Signal Transduction; Transcription Factor RelA

To explore the effect of aluminum phosphate gel and Kangfuxin on esophageal pathology and expressions of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in rats with reflux esophagitis and explore the possible mechanisms.. Sixty SD rats were randomized into aluminum phosphate gel group (n=10), Kangfuxin group (n=10), aluminum phosphate gel+Kangfuxin group (n=10), model group (n=20), and control group (n=10). Except for those in the control group, all the rats were subjected to infusion of diluted lysolecithin with hydrochloric acid in the esophagus for 14 days. Ten rats in the model group and those in the control group were sacrificed to examine the pathological changes and contents of IL-8 and PGE2 in the esophagus using optical and electron microscopes and radioimmunoassay. The next day the rest rats were given corresponding treatments (saline in model group) administered into the esophagus on a daily basis for 14 days, after which esophageal pathologies and IL-8 and PGE2 contents were examined.. The model rats showed obvious esophageal pathologies including inflammatory cell infiltration, vacuolar degeneration of the epithelial cells, esophageal erosion and even ulceration, with severe detachment of the epithelial cells. The rats in all the intervention groups showed lessened esophageal pathologies and lowered esophageal IL-8 and PGE2 contents compared with those in the model group. Esophageal mucosal injury index and IL-8 and PGE2 contents were all significantly lower in rats receiving combined treatment with aluminum phosphate and Kangfuxin than in those receiving either of the treatments (P<0.05).. Both Kangfuxin and aluminum phosphate gel are effective in the treatment for reflux esophagitis induced by lysolecithin and hydrochloric acid, and their therapeutic effects are achieved possibly by reducing IL-8 and PGE2 levels in the esophagus.

Topics: Aluminum Compounds; Animals; Dinoprostone; Disease Models, Animal; Drugs, Chinese Herbal; Esophagitis, Peptic; Esophagus; Gels; Interleukin-8; Phosphates; Rats; Rats, Sprague-Dawley

Barrett's esophagus (BE) is known to progress to esophageal adenocarcinoma in a setting of chronic inflammation. Toll-like receptor (TLR) 4 has been linked to inflammation-associated carcinogenesis. We aimed to determine the expression and functional activity of TLR4 in the esophagus and whether TLR4 activation in BE could promote carcinogenesis by inducing COX-2 expression.. TLR4 expression in esophageal adenocarcinoma, BE, duodenum, reflux esophagitis and normal squamous esophagus biopsies was assessed using real-time PCR and validated by in situ hybridization and immunohistochemistry. Ex vivo cultures of BE, duodenum and normal squamous esophagus biopsies and a BE cell line (BAR-T) were stimulated with the TLR4 agonist lipopolysaccharide (LPS). To evaluate the effect of TLR4 activation, NF-κB activation, IL8 secretion and expression and COX-2 expression were determined.. TLR4 expression was significantly increased in esophageal adenocarcinoma, BE, duodenum and reflux esophagitis compared to normal squamous esophagus. LPS stimulation resulted in NF-κB activation and a dose-dependent increase of IL8 secretion and mRNA expression. The induction of IL8 was more evident in BE compared to normal squamous esophagus. Upon LPS stimulation, COX-2 expression increased significantly in ex vivo cultured BE biopsies, which was observed in both epithelium and lamina propria cells. However, no effect was found in duodenum and normal squamous esophagus biopsies.. TLR4 activation in BE results in a strong increase in COX-2 and may contribute to malignant transformation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biopsy; Cyclooxygenase 2; Esophageal Neoplasms; Esophagitis, Peptic; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; NF-kappa B; Precancerous Conditions; RNA, Messenger; Tissue Culture Techniques; Toll-Like Receptor 4; Up-Regulation; Young Adult

Oesophagitis might result from the effects of chemokines produced by oesophageal cells in response to gastro-oesophageal reflux, and not solely from the direct, caustic effects of refluxed gastric juice. Proton pump inhibitors (PPI) can block chemokine production through mechanisms independent of their antisecretory effects. We studied omeprazole effects on chemokine production by oesophageal epithelial cells exposed to acidic bile salts.. Human primary and telomerase-immortalised oesophageal squamous cells were exposed to acidic bile salt medium with or without omeprazole pretreatment. Interleukin (IL)-8 expression was determined by RT-PCR and ELISA. IL-8 promoter activity was measured by luciferase reporter assay. Binding of NF-κB and AP-1 subunits to the IL-8 promoter was assessed by chromatin immunoprecipitation (ChIP) assay. Immune cell migration induced by conditioned medium was determined by a double-chamber migration assay system.. Acidic bile salt medium caused oesophageal epithelial cells to express IL-8 mRNA and protein by activating the IL-8 promoter through NF-κB and AP-1 binding. Omeprazole inhibited that acidic bile salt-stimulated IL-8 expression by blocking the nuclear translocation of p65 (an NF-κB subunit), and by blocking the binding of p65, c-jun and c-fos (AP-1 subunits) to the IL-8 promoter. Omeprazole also blocked the ability of conditioned medium from cells exposed to acidic bile salts to induce immune cell migration.. In oesophageal squamous epithelial cells, omeprazole inhibits IL-8 expression through effects on NF-κB and AP-1 that are entirely independent of effects on gastric acid secretion. These previously unrecognised PPI effects might contribute to the healing of reflux oesophagitis.

Topics: Bile Acids and Salts; Biomarkers; Cell Line; Cells, Cultured; Chromatin Immunoprecipitation; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Esophagitis, Peptic; Esophagus; Female; Humans; Interleukin-8; Male; Middle Aged; NF-kappa B; Omeprazole; Proton Pump Inhibitors; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor AP-1

Helicobacter pylori (H. pylori) infection induces cytokine production and is associated with gastrointestinal diseases. This study examined the relationship of gene polymorphisms, including interleukin (IL)-1beta, -10, -8, and tumor necrosis factor-alpha (TNF-alpha), H. pylori infection, and susceptibility to gastrointestinal disorders in Taiwanese patients.. IL-1beta-511/-31/+3953, -10-1082/-819/-592, -8-251, and TNF-alpha-308 polymorphisms were assessed in 628 gastrointestinal disease patients, and 176 healthy controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method.. IL-1beta-511 T/T and -31 C/C genotypes, and IL-1beta-511 T and -31 C alleles were associated with an increased risk of reflux esophagitis (P = 0.034, odds ratio [OR] = 1.384, 95% confidence interval [CI]: 1.023-1.871; P = 0.031, OR = 1.388, 95% CI: 1.028-1.873; P = 0.044, OR = 1.342, 95% CI: 1.008-1.786; and P = 0.040, OR = 1.349, 95% CI: 1.014-1.796, respectively). No relationship was found between H. pylori infection and the risk of reflux esophagitis. IL-10-819 C/T and -10-592 A/C genotypes and IL-10-1082/-819/-592 ATA/ACC and ATA/GCC haplotypes were associated with an increased risk of gastritis (P = 0.021, OR = 1.721, 95% CI: 1.084-2.733; P = 0.016, OR = 1.766, 95% CI: 1.112-2.805; P = 0.039, OR = 1.662, 95% CI: 1.024-2.697; and P = 0.035, OR = 1.600, 95% CI: 1.024-2.499, respectively).. Among Taiwanese patients, IL-1beta and -10 polymorphisms were associated with an increased risk of erosive reflux esophagitis and gastritis, respectively.

Topics: Adult; Asian People; Case-Control Studies; Chi-Square Distribution; Esophagitis, Peptic; Female; Gastritis; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-10; Interleukin-1beta; Interleukin-8; Linkage Disequilibrium; Logistic Models; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; Risk Assessment; Risk Factors; Taiwan; Tumor Necrosis Factor-alpha

Topics: Analysis of Variance; Biomarkers; Enzyme-Linked Immunosorbent Assay; Esophagitis, Peptic; Esophagoscopy; Esophagus; Female; Humans; Interleukin-8; Male; Mucous Membrane; Predictive Value of Tests; Proportional Hazards Models; Recurrence; Time Factors

Chronic inflammation of esophageal mucosa secondary to refluxed gastric juice increases gene expression of interleukin 8 (IL-8). Antireflux surgery can reduce this overexpression.. Prospective analysis of archival paraffin-embedded tissue.. Academic tertiary medical center.. One hundred eight patients with reflux symptoms were classified according to pH monitoring and endoscopic and histologic findings. Twenty patients did not have reflux or mucosal injury; 47 had reflux disease (16 esophagitis and 31 Barrett's esophagus), 20 had dysplasia, and 21 had adenocarcinoma. Microdissection was performed to exclude inflammatory cells and stromal tissue. After RNA isolation and reverse transcription, IL-8 messenger RNA expression was measured using quantitative real-time polymerase chain reaction. All patients with reflux disease had Nissen fundoplication with biopsies at matched levels within the esophagus preoperation and postoperation.. Expression of IL-8 was increased in patients with reflux compared with those without reflux. Patients with the highest IL-8 expression were those with Barrett's dysplasia and adenocarcinoma (P<.001). In patients with reflux, Nissen fundoplication led to significantly decreased IL-8 expression compared with preoperative levels in esophagitis (P = .01) and Barrett's esophagus (P = .03).. Interleukin 8 messenger RNA expression increases during the progression of reflux disease from normal squamous mucosa to esophageal adenocarcinoma. Elimination of reflux with Nissen fundoplication significantly reduces IL-8 expression in both squamous and Barrett's mucosa. These results demonstrate that effective antireflux surgery can modulate the gene expression of esophageal mucosa and may impact the natural history of reflux disease.

Topics: Adenocarcinoma; Barrett Esophagus; Case-Control Studies; Esophageal Neoplasms; Esophagectomy; Esophagitis, Peptic; Fundoplication; Gastroesophageal Reflux; Humans; Interleukin-8; RNA, Messenger

It has been reported that inflammatory cell infiltration can be detected in patients with endoscopically negative gastroesophageal reflux disease (GERD) as well as those with erosive reflux esophagitis. In this study, we examined the expression of mRNA for interleukin (IL)-8, a potent chemokine for neutrophils, in the esophageal mucosa of patients with GERD and compared the results with their endoscopic findings and symptoms.. Biopsy samples were obtained from 80 patients. Endoscopic diagnosis was performed according to the Los Angeles classification. Patients with typical symptoms such as heartburn despite normal endoscopic findings were classified as the non-erosive GERD group. Total cellular RNA was extracted from the biopsy samples and IL-8 mRNA was quantified by real-time polymerase chain reaction (PCR). Localization of IL-8 protein in the esophageal mucosa was done by immunostaining.. Expression of IL-8 mRNA was correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration, but not with the symptoms of the patients. Expression of IL-8 mRNA was also detected in all patients with non-erosive GERD. The level of IL-8 expression in non-erosive GERD was low compared with that in erosive GERD, but was higher than that in normal controls. IL-8 immunostaining was found in the basal layers of the esophageal mucosa. Administration of lansoprazole, a proton-pump inhibitor, decreased both IL-8 mRNA and protein levels in the esophageal mucosa.. These results suggest that IL-8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non-erosive GERD.

Topics: Base Sequence; Biopsy, Needle; Endoscopy, Gastrointestinal; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-8; Male; Molecular Sequence Data; Mucous Membrane; Polymerase Chain Reaction; Probability; Prognosis; Prospective Studies; RNA, Messenger; Sampling Studies; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

Chemokines play a key role in the pathogenesis of various inflammatory conditions. However, there is little information on their profile in reflux esophagitis (RE). We sought to study esophageal mucosa levels of chemokines in RE.. A total of 32 outpatients with RE and 13 normal controls were studied. Endoscopic severity of RE was classified according to the Los Angeles grading system. Paired biopsy specimens were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of mucosal levels of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and IL-1 beta by enzyme linked immunosorbent assays, while the other was formalin-fixed for histopathological evaluation.. IL-8, MCP-1, and RANTES levels were significantly higher in esophageal mucosa of RE patients than those of the controls. IL-8 levels correlated significantly with the endoscopic severity of RE. Basal zone hyperplasia and papillary elongation, histopathological hallmarks of RE, were both associated with higher levels of IL-8 and MCP-1. The presence of intraepithelial neutrophils and eosinophils, which also indicate RE, was associated with high levels of IL-8 and RANTES, respectively. There were no significant differences in IL-1 beta levels between the RE and control groups, but IL-1 beta levels correlated significantly with the IL-8 production. Again, the IL-8 levels were significantly decreased after lansoprazole treatment.. Our results indicate that chemokines produced locally in the esophageal mucosa may be involved in the development and progression of RE.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Chemokine CCL2; Chemokine CCL5; Chemokines; Enzyme-Linked Immunosorbent Assay; Esophagitis, Peptic; Esophagus; Female; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Middle Aged; Mucous Membrane; Severity of Illness Index

Recent studies have shown that acid-suppressive therapy increases the severity of Helicobacter pylori- associated gastritis in the corpus.. To evaluate interleukin (IL)-8 production in the gastric corpus mucosa before and during acid-suppressive therapy in H pylori-infected patients.. Ten patients with reflux esophagitis (five H pylori-positive and five H pylori-negative) were treated with omeprazole 20 mg. Serum gastrin concentrations, H pylori colonization density and mucosal IL-8 levels in the corpus were investigated at entry and two weeks after starting therapy. IL-8 levels were measured by ELISA. The organism density was determined, and scored according to area occupied by the bacterial colonies. The presence of H pylori was assessed by rapid urease testing and histological finding of gastric biopsy specimens.. In H pylori-positive patients, concentrations of IL-8 during therapy significantly exceeded those before therapy (36.2+/-6. 8 versus 18.3+/-3.8 pg/mg protein; P<0.05) without altering H pylori density. In H pylori-negative patients, IL-8 levels were similar before and during therapy (6.1+/-2.7 versus 6.3+/-3.0 pg/mg protein). Concentrations of gastrin during therapy were significantly higher than those before therapy in all patients.. The results suggest that acid suppression increases mucosal IL-8 levels in H pylori-infected patients with reflux esophagitis.

Topics: Adult; Aged; Enzyme Inhibitors; Esophagitis, Peptic; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Middle Aged; Omeprazole