interleukin-8 and Metaplasia

Chronic gastritis is a kind of chronic gastric mucosal inflammation caused by many factors.Intestinal metaplasia refers to the transformation of gastric mucosal epithelial cells into small/large intestinal mucosal epithelium containing Panette or goblet cells.Chronic gastritis has the highest incidence among stomach diseases,while intestinal metaplasia is the serious manifestation of chronic gastritis.In this experiment,the therapeutic effect of modified Zhengqi Powder on mild intestinal metaplasia in chronic gastritis and on patients' quality of life and inflammatory reaction was investigated to analyze the efficacy and mechanism of traditional Chinese medicine prescription.From April 2016 to April 2017,120 patients of chronic gastritis with mild intestinal metaplasia were selected and divided into two groups according to the envelope method.The control group(60 cases) was treated with famoxetine.After one month of continuous treatment,the total effective rate of treatment in the observation group was 93.3%,which was much higher than 80.0% in the control group.Health questionnaire(SF-36),serum C-reactive protein(CRP),interleukin-8(IL-8) and tumor necrosis factor-α(TNF-α) levels were significantly higher than those in the control group(P<0.05).The results showed that modified Zhengqi Powder has a significant efficacy in treat chronic gastritis with mild intestinal metaplasia,and can obviously alleviate clinical symptoms and intestinal metaplasia,remove inflammatory factors and improve the quality of life of patients,and is worth promotion.

Topics: C-Reactive Protein; Drugs, Chinese Herbal; Gastric Mucosa; Gastritis, Atrophic; Humans; Interleukin-8; Metaplasia; Quality of Life; Tumor Necrosis Factor-alpha

to investigate the serum levels of TNF-a, IL-8, VEGF in Helicobacter pylori infection, and their association with the degrees of gastritis histopathology.. a cross-sectional study was done on 80 consecutive gastritis patients admitted to endoscopy units at Adam Malik General Hospital and Permata Bunda Hospital, Medan, Indonesia from July-December 2014. The Rapid Urease test was used for the diagnosis of H. pylori infection. The severity of chronic inflammation, neutrophil infiltration, atrophy, and intestinal metaplasia were assessed. Serum samples were obtained to determine circulating TNF-a, IL-8, and VEGF. Univariate and bivariate analysis (chi square, fisher's exact, and mann-whitney test) were done using SPSS version-22.. there were 41.25% of 80 patients infected with Helicobacter pylori. Serum TNF-a and VEGF levels in the infected group were significantly higher compared to H. pylori negative, but there were no significant differences between serum levels of IL-8 in H. pylori positive and negative. There were significant associations between serum level of TNF-a and IL-8 with degree of chronic inflammation, and also between serum level of IL-8 and degree of neutrophil infiltration. There were significant associations between serum level of VEGF and degree of atrophy, and also between serum level of VEGF and degree of intestinal metaplasia.. High levels of TNF-a were associated with severe degree of chronic inflammation, high levels of IL-8 associated with severe degree of chronic inflammation and neutrophil infiltration, and high levels of VEGF associated with severe degree of premalignant gastric lesion.

Topics: Adult; Cross-Sectional Studies; Endoscopy, Gastrointestinal; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Indonesia; Inflammation; Interleukin-8; Male; Metaplasia; Middle Aged; Neutrophil Infiltration; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Chronic gastritis associated with Helicobacter pylori is a leading cause of gastric intestinal metaplasia (IM), which arises from abnormal cell differentiation of the epithelium in the gastric mucosa. However, the mechanisms involved in H. pylori-mediated IM remain elusive. The aim of our study was to explore the effects and the underlying mechanisms of H. pylori on the abnormal expression of Hath1 and Sox2 and to reveal its relationship to the development of gastric IM. We found that Hath1 and Sox2 were overexpressed in gastric IM tissue. Hath1 expression was up-regulated, whereas Sox2 expression, which was independent of the CagA virulence factor, was down-regulated in gastric epithelial cells and coincided with increased IL-6 and IL-8 levels in the culture media. Stimulation with H. pylori-related cytokine IL-8, but not IL-6 or IL-1β, was induced by Hath1 expression in the gastric epithelial cells. Although IL-8 and IL-6 levels correlated with STAT3 (signal transducer and activator of transcription) phosphorylation before and after H. pylori eradication in the gastric mucosa, only the blocking of IL-8-induced STAT3 activation using AG490 or STAT3-targeting RNA interference altered Hath1 expression. Additionally, we found that H. pylori down-regulated Hes1, which is a direct downstream target gene of Notch signaling and a repressor of Hath1 expression. These findings suggest that H. pylori induced inflammation up-regulate Hath1 expression via interleukin-8/STAT3 (IL-8) phosphorylation while suppressing Hes1, which provides a novel molecular connection between a H. pylori infection and intestinal metaplasia.

Topics: Antigens, Bacterial; Bacterial Proteins; Basic Helix-Loop-Helix Transcription Factors; Cell Line, Tumor; Coculture Techniques; Dose-Response Relationship, Drug; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Homeodomain Proteins; Humans; Immunity, Mucosal; Immunohistochemistry; Interleukin-6; Interleukin-8; Metaplasia; Phosphorylation; Prospective Studies; RNA Interference; STAT3 Transcription Factor; Transcription Factor HES-1; Tyrphostins

Chronic infection of Helicobacter pylori in the stomach mucosa with translocation of the bacterial cytotoxin-associated gene A (CagA) effector protein via the cag-Type IV secretion system (TFSS) into host epithelial cells are major risk factors for gastritis, gastric ulcers, and cancer. The blood group antigen-binding adhesin BabA mediates the adherence of H. pylori to ABO/Lewis b (Le(b)) blood group antigens in the gastric pit region of the human stomach mucosa. Here, we show both in vitro and in vivo that BabA-mediated binding of H. pylori to Le(b) on the epithelial surface augments TFSS-dependent H. pylori pathogenicity by triggering the production of proinflammatory cytokines and precancer-related factors. We successfully generated Le(b)-positive cell lineages by transfecting Le(b)-negative cells with several glycosyltransferase genes. Using these established cell lines, we found increased mRNA levels of proinflammatory cytokines (CCL5 and IL-8) as well as precancer-related factors (CDX2 and MUC2) after the infection of Le(b)-positive cells with WT H. pylori but not with babA or TFSS deletion mutants. This increased mRNA expression was abrogated when Le(b)-negative cells were infected with WT H. pylori. Thus, H. pylori can exploit BabA-Le(b) binding to trigger TFSS-dependent host cell signaling to induce the transcription of genes that enhance inflammation, development of intestinal metaplasia, and associated precancerous transformations.

Topics: Adhesins, Bacterial; Animals; Bacterial Adhesion; Bacterial Secretion Systems; Chemokine CCL5; CHO Cells; Cricetinae; Cricetulus; Dogs; Gastric Mucosa; Gene Deletion; Helicobacter Infections; Helicobacter pylori; Homeodomain Proteins; Humans; Inflammation; Interleukin-8; Lewis Blood Group Antigens; Metaplasia; Mucin-2; Precancerous Conditions; Signal Transduction

To investigate the effects of interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF) gene polymorphisms, Helicobacter pylori (H. pylori) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM).. A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progression group (no histological progression from normal or superficial gastritis, n = 137), group I (progressed from normal or superficial gastritis to SCAG, n = 134) and group II (progressed from normal or superficial gastritis to IM, n = 101). IL-8, MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing.. An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection.. IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.

Topics: Adult; Aged; Cohort Studies; Cytokines; Female; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Intestines; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Male; Metaplasia; Middle Aged; Polymorphism, Genetic; Risk Factors; Stomach Neoplasms; Young Adult

Helicobacter pylori (H. pylori) is an important risk factor of gastric adenocarcinoma. Interleukin (IL)-8 is a potent angiogenic factor and plays an important role in inflammation of gastric mucosa by H. pylori. Host susceptibility may help to predict H. pylori-infected individuals with a higher risk of gastric adenocarcinoma. The aim of this study was to clarify the effect of IL-8 polymorphism on angiogenesis in the process of gastric carcinogenesis in H. pylori-infected Koreans. The IL-8-251A/T polymorphism was genotyped by PCR-RFLP from a total of 395 subjects; 92 normal controls, 87 H. pylori-infected controls, 108 chronic atrophic gastritis and/or intestinal metaplasia and 108 adenocarcinoma. The gastric mucosal concentrations of IL-8, membrane metalloproteinase (MMP)-9, angiopoietin (Ang)-1, and vascular endothelial growth factor (VEGF) were measured by ELISA. MMP-9 concentrations were increased with disease progression. There was significant correlation between MMP-9 and disease progression in AA (r=0.42, p<0.01) and AT genotype (r=0.43, p<0.01). Ang-1 concentrations were increased in AA genotype (r=0.40, p=0.01). However, there was no significant correlation between VEGF and disease progression in AA genotype. In conclusion, IL-8-251 AA genotype may be associated with angiogenesis in gastric carcinogenesis in H. pylori-infected Koreans.

Topics: Adenocarcinoma; Adult; Aged; Angiopoietin-1; Asian People; Disease Progression; Female; Gastric Mucosa; Gastritis, Atrophic; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Korea; Male; Matrix Metalloproteinase 9; Metaplasia; Middle Aged; Neovascularization, Pathologic; Polymorphism, Genetic; Stomach Neoplasms; Vascular Endothelial Growth Factor A

Chronic inflammation associated with Helicobacter pylori infection is a risk factor of gastric adenocarcinoma. Interleukin-8 (IL-8) plays an important role in gastric mucosal inflammation induced by H. pylori infection. Recently, studies on the association of genetic polymorphisms of various proinflammatory cytokines with gastric carcinogenesis showed varying results on the basis of the ethnicity. We conducted this study to investigate the association of IL-8-251 A/T polymorphism with gastric carcinogenesis in H. pylori-infected Koreans.. The IL-8-251 A/T polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism using DNA from a total of 605 H. pylori-infected subjects; 206 controls, 149 chronic atrophic gastritis and/or intestinal metaplasia, 97 gastric dysplasia, and 153 gastric adenocarcinoma. Degrees of gastric mucosal inflammation and mucosal IL-8 level were also assessed.. The IL-8-251 A carriers showed a higher risk of gastric adenocarcinoma (adjusted odds ratio 2.06, 95% confidence interval 1.16-3.68) than IL-8-251 T/T genotypes. The IL-8-251 A allele was also significantly associated with the degree of neutrophil infiltration, atrophy, and intestinal metaplasia in a younger age group. Among the chronic atrophic gastritis and/or intestinal metaplasia group, mucosal IL-8 level was significantly higher in subjects with IL-8-251 A allele than those with IL-8-251 T/T genotypes (P=0.011).. The IL-8-251 A allele is associated with higher IL-8 production, more severe inflammation, mucosal atrophy, and intestinal metaplasia than IL-8-251 T/T genotype in H. pylori-infected hosts. The IL-8-251 A allele may also increase the risk of gastric adenocarcinoma through an enhanced inflammatory process in H. pylori-infected Koreans.

Topics: Adenocarcinoma; Age Factors; Analysis of Variance; Asian People; Female; Gastric Mucosa; Gastritis, Atrophic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Korea; Male; Metaplasia; Middle Aged; Odds Ratio; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Sex Factors; Stomach Neoplasms

Genetic variations of the inflammatory IL-8 and TNF-alpha genes can influence the outcome of gastric alterations. Our aims were to determine the prevalence and effect of the T-251A functional polymorphism of IL-8 and the G-308A polymorphism of TNF-alpha in histological and macroscopic gastric diseases related to Helicobacter pylori infection.. Genomic DNA was extracted from biopsy samples from patients with gastritis (n=86, H. pylori positive=41), atrophy (n=32, H. pylori positive=13), intestinal metaplasia (IM) (n=43, H. pylori positive=22) and from histologically negative patients (n=57). The samples were divided by macroscopic diagnosis into erosion and negative groups. The T-251A polymorphism was examined with the amplification refractory mutation system method; the G-308A polymorphism was determined by the polymerase chain reaction-restriction fragment length polymorphism method. For statistical evaluation, Fischer's exact test was used.. In the case of T-251A of IL-8, the frequency of the A/A genotype was significantly increased in gastritis (P=0.049) and IM (P=0.038) groups as compared with the histologically negative ones. No relationship was found between macroscopic erosions and H. pylori infection. In the case of G-308A, the G/G genotype frequency was statistically increased in erosions as compared with negative groups (P=0.035). No difference in the distribution of G-308A genotypes in relation to histological alterations and the H. pylori infection was observed.. The effect of the polymorphism of IL-8 seems to be relevant in the pathogenesis of histological gastritis and IM, and the effect of the polymorphism of TNF-alpha is relevant in the pathogenesis of macroscopic erosive gastritis.

Topics: Atrophy; Gastritis; Genetic Predisposition to Disease; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Metaplasia; Polymorphism, Genetic; Stomach; Tumor Necrosis Factor-alpha

To study whether H pylori are associated with chronic cholecystitis.. The subjects were divided into three groups: H pylori-infected cholecystitis group, H pylori-negative cholecystitis group and control group. Pathologic changes of the gallbladder were observed by optic and electronic microscopes and the levels of interleukin-1, 6 and 8 (IL-1, 6 and 8) were detected by radioimmunoassay.. Histological evidence of chronic cholecystitis including degeneration, necrosis, inflammatory cell infiltration, were found in the region where H pylori colonized. Levels of IL-1, 6 and 8 in gallbladder mucosa homogenates were significantly higher in H pylori-infected cholecystitis group than those in H pylori-negative cholecystitis group and control group.. H pylori infection may be related to cholecystitis.

Topics: Case-Control Studies; Cholecystitis; Chronic Disease; Gallbladder; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Metaplasia; Mucous Membrane

The incidence of esophageal adenocarcinoma has increased significantly in the western world over the last 20 yr. Most cases arise in a background of chronic gastroesophageal reflux, and specialized intestinal metaplasia in Barrett's esophagus is frequently an antecedent phenotype or evident in association with adenocarcinoma. The molecular events that characterize the pathway from inflammation to metaplasia to dysplasia and adenocarcinoma are poorly understood.. To examine the expression of the proinflammatory cytokines IL-8 and IL-1beta along the esophagitis, metaplasia, dysplasia, and adenocarcinoma pathway, and to correlate this with histological changes and expression of the transcription factor NF-kappaB.. Fresh biopsy specimens were collected from patients with reflux esophagitis (n=15), Barrett's esophagus (n=35), Barrett's adjacent to adenocarcinoma (n=8), and esophageal adenocarcinoma (n=35). IL-8 and IL-1beta expression were measured using enzyme-linked immunosorbent assay. NF-kappaB expression was measured by electrophoretic mobility shift assay.. Elevated expression of NF-kappaB was found in 2 (13%) out of 15 patients with reflux esophagitis, 21 (60%) out of 35 patients with Barrett's esophagus, and 28 (80%) out of 35 patients with esophageal adenocarcinoma. All 5 patients with Barrett's esophagus and high-grade dysplasia showed elevated expression of NF-kappaB. IL-8 and IL-1beta were significantly increased in esophagitis, Barrett's, and adenocarcinoma compared with squamous epithelium, and in adenocarcinoma compared with all other groups. There was a stepwise increase in the expression of IL-8, IL-1beta, and NF-kappaB from normal through Barrett's epithelium to adenocarcinoma in eight cases of esophageal adenocarcinoma. The levels of both IL-8 and IL-1beta in adenocarcinoma patients correlated with stage of disease. Patients with adenocarcinoma who were NF-kappaB positive had significantly higher levels of both IL-8 (p=0.04) and IL-1beta (p=0.03) compared to adenocarcinoma patients who were NF-kappaB negative.. The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers; Biopsy; Electrophoresis; Endoscopy, Digestive System; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagitis; Female; Gastroesophageal Reflux; Humans; Interleukin-1; Interleukin-8; Intestinal Mucosa; Male; Metaplasia; Middle Aged; NF-kappa B; Precancerous Conditions; Prospective Studies

There is no direct evidence for an animal model of Helicobacter pylori induced duodenal ulcer.. In this study we evaluated the roles of bacterial strain and age of experimental animals in induction of duodenitis and duodenal ulcer in Mongolian gerbils after H pylori infection.. Specific pathogen free Mongolian gerbils were inoculated orally with three bacterial strains (H pylori ATCC 43504, TN2GF4, and K-6, a clinical isolate from a patient with gastric cancer in our clinic). These strains have both the cagA gene and VacA. Five week old gerbils were used to emulate prematurity infection and 14 week old animals were used as mature test subjects. Animals were observed for 12 weeks after inoculation. Interleukin 8 (IL-8) production in gastric epithelial cells (MKN74) after coculture with the H pylori strains was measured by ELISA.. Gastritis and gastric ulcers were found in all gerbils infected with the three strains. However, duodenitis and gastric metaplasia were seen more frequently in gerbils infected with TN2GF4 and K-6 strains than in the ATCC 43504 infected or control groups (p<0.05). Superficial duodenal ulcers with severe duodenitis and gastric metaplasia were found in two gerbils inoculated at 14 weeks with the TN2GF4 strain but none at five weeks. The TN2GF4 strain stimulated significantly higher levels of IL-8 than ATCC 43504 and K6 strains (p=0.0039).. When injected into adult Mongolian gerbils, a specific strain (TN2GF4) of H pylori can induce duodenitis with gastric metaplasia and superficial duodenal ulcers. Induction of duodenal ulcer in an animal model fulfills the requirements of Koch's postulates for establishing a role for H pylori as a causative agent.

Topics: Age Factors; Animals; Coculture Techniques; Disease Models, Animal; Duodenal Ulcer; Duodenitis; Gastric Mucosa; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Interleukin-8; Male; Metaplasia

To evaluate the relationship between mitochondrial DNA instability (mtMSI) and interleukin-8 (IL-8) activity in gastric mucosa of various lesions.. IL-8 level in gastric mucosa was assayed using ELISA method. The mtMSI was detected by PCR-SSCP techniques.. mtMSI was observed in 11 out of 30 (36.7%) gastric cancers, 2 of 15 (13.3%) intestinal metaplasia, 2 of 10 dysplasia and 1 of 10 chronic atrophic gastritis. IL-8 level in mtMSI+ group [(76.8 +/- 3.8) pg/mg] was significantly higher than that in mtMSI- group [(48.3 +/- 3.6) pg/mg, P < 0.05].. mtMSI closely correlates with IL-8 level in gastric mucosa and is involved in gastric carcinogenesis.

Topics: DNA, Mitochondrial; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Gastritis, Atrophic; Genomic Instability; Humans; Interleukin-8; Metaplasia; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Precancerous Conditions; Stomach Neoplasms

Presence of the Helicobacter pylori adherence factor blood group Ag-binding adhesin (BabA; binding to Lewis(b) (Le(b))) is associated with ulcer disease, adenocarcinoma, and precancerous lesions. The importance of BabA for bacterial colonization and the inflammatory response is unknown. A total of 141 antral biopsies from H. pylori-infected patients were assessed in regard to the degree of granulocytic (G0 degrees--G3 degrees) and lymphocytic (L1 degrees--L3 degrees) infiltration. DNA genotypes of babA2 (the transcriptionally active gene of BabA), cagA, and vacAs1/2 were determined by PCR. Colonization density and Le(b) status on gastric epithelial cells were determined by immunohistochemistry. Real-time quantitative (TaqMan) RT-PCR determined mRNA expression of IL-8, TNF -alpha, and the Th1 markers IFN-gamma and the IL-12R beta2 chain. A total of 91% of infected patients were Le(b) positive. The vacAs1(+)/cagA(+) strains harboring babA2 showed significantly higher levels of granulocytic infiltration, bacterial colonization, and IL-8 mRNA than vacAs1(+)/cagA(+) strains lacking babA2. IL-8 mRNA and protein production by KATO III cells in vitro increased dose dependently with addition of different numbers of type 1 strains (G27 and 2808 strains, 0.1--20 bacteria/cell). The mRNA expression of TNF-alpha, IFN-gamma, and IL-12R beta2 was higher in H. pylori-positive patients than in controls, but it did not differ significantly between patients infected with different strain types. These data suggest that BabA facilitates colonization of H. pylori and thereby increases IL-8 response, resulting in enhanced mucosal inflammation. Infection with strains harboring BabA thereby augment a nonspecific immune response, whereas the Th1 response toward H. pylori appears to be independent of BabA, cytotoxin-associated gene A, or vacuolating cytotoxin.

Topics: Adhesins, Bacterial; Adjuvants, Immunologic; Adult; Aged; Aged, 80 and over; Atrophy; Carrier Proteins; Cell Line; Cell Movement; Colony Count, Microbial; Female; Gastric Mucosa; Genes, Bacterial; Genotype; Granulocytes; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Interleukin-8; Intestines; Lewis Blood Group Antigens; Male; Metaplasia; Middle Aged; Oligosaccharides; Pyloric Antrum; Th1 Cells

Mucus hypersecretion contributes to the morbidity and mortality in acute asthma. Both T helper 2 (Th2) cytokines and epidermal growth factor receptor (EGFR) signaling have been implicated in allergen-induced goblet cell (GC) metaplasia. Present results show that a cascade of EGFR involving neutrophils is implicated in interleukin (IL)-13-induced mucin expression in GC. Treatment with a selective EGFR tyrosine kinase inhibitor prevented IL-13-induced GC metaplasia dose dependently and completely. Instillation of IL-13 also induced tumor necrosis factor-alpha protein expression, mainly in infiltrating neutrophils. Control airway epithelium contained few leukocytes, but intratracheal instillation of IL-13 resulted in time-dependent leukocyte recruitment by IL-13-induced IL-8-like chemoattractant expression in airway epithelium. Pretreatment with an inhibitor of leukocytes in the bone marrow (cyclophosphamide) or with a blocking antibody to IL-8 prevented both IL-13-induced leukocyte recruitment and GC metaplasia. These findings indicate that EGFR signaling is involved in IL-13-induced mucin production. They suggest a potential therapeutic role for inhibitors of the EGFR cascade in the hypersecretion that occurs in acute asthma.

Topics: Animals; Antibodies, Blocking; Chemotaxis, Leukocyte; Cyclophosphamide; Dose-Response Relationship, Drug; Enzyme Inhibitors; ErbB Receptors; Goblet Cells; Immunosuppressive Agents; Interleukin-13; Interleukin-8; Male; Metaplasia; Mucins; Neutrophil Activation; Protein-Tyrosine Kinases; Rats; Rats, Inbred F344; Respiratory Mucosa; Specific Pathogen-Free Organisms; Th2 Cells; Tumor Necrosis Factor-alpha

Although increased levels of interleukin (IL)-8 are known to be associated with infiltration of neutrophils in the gastric mucosa with Helicobacter pylori infection, no study has investigated the relationship between local IL-8 levels and neutrophil infiltration in the duodenal mucosa of patients with duodenal ulcer (DU).. Duodenal mucosal biopsy specimens with and without gastric metaplasia (GM) were obtained from patients with DU and controls with an endoscopic methylene blue (MB) staining method. Levels of IL-8 secreted in the organ cultures of biopsy specimens were measured with an enzyme-linked immunosorbent assay. The number of myeloperoxidase-positive neutrophils infiltrating the lamina propria was determined in immunohistochemically stained tissue sections.. Histologic assessment showed that there was a strong correlation between the absence of endoscopic MB staining and the extent of GM. The levels of IL-8 in both duodenal and antral mucosal tissues were significantly higher in patients with H. pylori infection than in those without infection. In patients with DU the duodenal mucosal tissues with GM (MB-unstained mucosa) showed significantly higher levels of IL-8 than those without GM (MB-stained mucosa) or the antral mucosa. The number of neutrophils showed similar variations among DU and control patients with a positive correlation with IL-8 activity. The levels of IL-8 and the number of neutrophils decreased after H. pylori eradication in both duodenal and antral mucosal tissues, and these changes were more remarkable in the duodenal mucosal tissues with GM.. Increased IL-8 activity in the duodenal mucosa with GM may be important for ulcerogenesis in H. pylori-positive DU patients.

Topics: Adult; Aged; Biopsy; Duodenal Ulcer; Endoscopy, Digestive System; Enzyme-Linked Immunosorbent Assay; Female; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Intestinal Mucosa; Leukocyte Count; Male; Metaplasia; Middle Aged; Neutrophils; Stomach

Topics: Bronchi; Bronchitis; Cell Degranulation; Chronic Disease; Exocrine Glands; Humans; Interleukin-8; Leukocyte Elastase; Metaplasia; Mucus; Neutrophils; Sensory Receptor Cells; Sputum

Implantation of abraded polyethylene intramammary devices (IMD) for six months in the mammary glands of cows resulted in macroscopic and microscopic pathological changes in udder tissue. These changes were characterised by hyperplasia and metaplasia of the epithelial cells and hypertrophy of the subepithelial connective tissue examined by light and electron microscopy (EM). Quarters containing IMDs also had increased numbers of neutrophils and macrophages in the subepithelial stroma compared with control quarters. IMDs recovered six months after implantation were shown by transmission and scanning EM to be covered with plaque and cells. These cells were mainly macrophages, although other leucocytes were also present. In vitro culture of recovered IMDs in the presence of lipopolysaccharide resulted in the release of neutrophil chemotactic factor, or factors, and interleukin-1. Some quarters with IMDs also had concurrent infections at the time of slaughter. In these cases both the pathological changes seen in the tissues and the release of soluble mediators following in vitro culture of the IMDs were significantly increased compared with sterile quarters containing IMD.

Topics: Animals; Cattle; Cattle Diseases; Chemotactic Factors; Epithelium; Female; Hyperplasia; Hypertrophy; Interleukin-1; Interleukin-2; Interleukin-8; Interleukins; Mammary Glands, Animal; Metaplasia; Microscopy, Electron; Neutrophils; Prostheses and Implants