Effect of Helicobacter pylori infection on cyclooxygenase‐2 expression in gastric antral mucosa

OBJECTIVE: Helicobacter pylori infection is a major etiological cause of chronic gastritis. Inducible cyclooxygenase (COX‐2) is an important regulator of mucosal inflammation. Recent studies indicate that expression of COX‐2 may contribute to gastro­intestinal carcinogenesis. The aim of this study was to investigate the effects of H. pylori infection and eradication therapy on COX‐2 expression in gastric antral mucosa. METHODS: Antral biopsies were taken from 46 H. pylori‐infected patients, who also had chronic gastritis, both before and after anti‐H. pylori treatment. The COX‐2 protein was stained by using immunohistochemical methods and COX‐2 expression was quantified as the percentage of epithelial cells expressing COX‐2. Gastritis and H. pylori infection status were graded according to the Sydney system. RESULTS: Cyclooxygenase‐2 expression was detected in the cytoplasm of gastric antral epithelial cells both before and after the eradication of H. pylori. Cyclooxygenase‐2 expression in mucosa with H. pylori infection was compared with the corresponding mucosa after successful H. pylori eradication (20.1 ± 13.1%vs 13.8 ± 5.9%; P < 0.05). At the same time, COX‐2 expression in H. pylori‐infected mucosa was com­pared with the normal controls (18.0 ± 14.1%vs 12.3 ± 4.6%, P < 0.05). Expression of COX‐2 was correlated with the degree of chronic inflammation (r= 0.78, P < 0.05). CONCLUSIONS: Our results showed that H. pylori infection leads to gastric mucosal overexpression of COX‐2 protein, suggesting that the enzyme is involved in H. pylori‐related gastric pathology in humans.     

Helicobacter pylori infection accelerates human gastric mucosal cell proliferation

Helicobacter pylori causes chronic atrophic gastritis and intestinal type gastric cancer arises against a background of atrophic gastritis. Increased proliferation of epithelial cells is an important indicator of increased risk for gastric adenocarcinoma. We investigated gastric mucosal cell proliferation inH. pylori-associated gastritis and the effect of eradication therapy on this proliferation in 45 patients endoscopically diagnosed (31 with persistent eradication and 14 in whomH. pylori) recurred.H. pylori status was determined by culture and histology in biopsied specimens from the gastric antrum and corpus. Eradication of the infection was defined as reversal to negative on both tests. In vitro Ki-67 immunostaining of endoscopic biopsy specimens was used to measure mucosal cell proliferation inH. pylori-associated gastritis before and after therapy. The proliferative zone was defined as the distance of Ki-67-positive gastric epithelial cells between the highest and the lowest cells. In patients in whomH. pylori was eradicated, cell proliferation in both the antral and corpus mucosa had decreased 4 weeks after completion of the eradication therapy (P<0.01,P<0.001), and 6 months later, it had markedly decreased (P<0.05,P<0.05) and returned to normal. In patients in whomH. pylori recurred, only antral epithelial cell proliferation was reduced 4 weeks after eradication therapy, but whenH. pylori recurred, determined by culture and histology, cell proliferation level was the same as that before eradication. These results suggest thatH. pylori infection accelerates cell proliferation in gastric mucosa and may play a causal role in the chain of events leading to gastric carcinoma.     

Pathological development of the gastric mucosa in Helicobacter pylori‐related diseases

OBJECTIVE : To study the relationship between Helicobacter pylori eradication and the pathological development of the gastric mucosa in H. pylori‐related diseases. METHODS : One hundred and ninety‐one H. pylori‐infected patients were randomly given anti‐H. pylori or non‐anti‐H. pylori medications. Endoscopic examination was carried out 1 year after treatment. Pathological classifications followed the Sydney System. RESULTS : Of the 191 patients, those with chronic inflammation of the gastric mucosa improved (P < 0.05), as did those with atrophy and intestinal metaplasia (P < 0.05). Helicobacter pylori was eradicated in 107 patients, but not in 84 patients. Compared with those patients in whom H. pylori was not eradicated, those with H. pylori eradicated had ameliorated chronic inflammation of the gastric mucosa (P < 0.05) and active inflammation reduced in some cases (P < 0.05). Notwithstanding a stratification of different gastric diseases and different treatments, patients with H. pylori eradicated showed a more marked improvement in mucosal chronic inflammation than did patients in whom H. pylori was not eradicated (P < 0.05). CONCLUSIONS : These results suggest that H. pylori infection is closely related to active inflammation of the gastric mucosa. Helicobacter pylori eradication is beneficial in improving chronic inflammation of the gastric mucosa.     

Long-term follow-up of gastric histology after Helicobacter pylori eradication

Helicobacter pylori causes chronic active gastritis and is thought to be associated with the development of gastric atrophy, intestinal metaplasia and carcinoma. As the effect of H. pylori eradication on this process is poorly understood, we sought to determine the long-term effects of H. pylori eradication on gastric histology. Fifty-four patients with duodenal ulceration associated with H. pylori infection received H. pylori eradication therapy in 1985/86 and either remained infected (n= 22) or had the infection eradicated (n= 32); patients were followed up by endoscopy with gastric antral biopsy for 7.1 years (mean). Histopathological analysis of gastric antral mucosa from patients rendered H. pylori-negative revealed a marked decrease in both inflammatory cells within the lamina propria and intraepithelial neutrophils and an increase in epithelial mucinogenesis. Gland atrophy remained unchanged in both H. pylori-positive and -negative patients. When examined for the presence and severity of intestinal metaplasia, there was neither a difference between the two patient groups nor a change with time. These data demonstrate that significant long-term improvements in gastric histology accompany H. pylori eradication when compared with histology in patients with persistent infection. Whether this confers a protective effect by reducing the risk of gastric carcinoma remains unknown.     

Inflammation of the gastric remnant after gastrectomy: mucosal erythema is associated with bile reflux and inflammatory cellular infiltration is associated with Helicobacter pylori infection

Background Controversy exists concerning the role of bile reflux and Helicobacter pylori (H. pylori) infection in the development of inflammation of the gastric remnant after gastrectomy. This study was designed to investigate association of bile reflux and H. pylori infection or both with inflammatory changes in the gastric remnant.Methods A questionnaire on GI symptoms was returned by 200 gastrectomy patients, and 24-h bilirubin monitoring in the gastric remnant was performed on 55 patients with Bilitec 2000. Upper GI endoscopy evaluated reflux gastritis in the gastric remnant, and the presence of H. pylori infection and chronic, active inflammatory cellular infiltration in the biopsy specimens were examined microscopically with the updated Sydney system.Results No difference in the incidence of GI symptoms was observed among individual gastrectomy patients. Bile reflux was lower in patients who had undergone a gastrectomy with jejunal interposition, a pylorus-preserving gastrectomy, and a gastrectomy with Roux–Y anastomosis than those who had undergone a Billroth-II (B-II) anastomosis (P < 0.05). Endoscopy showed positive correlation between mucosal erythema and bile reflux (P < 0.001). No correlation was observed between the mucosal erythema and chronic and active inflammatory cellular infiltration. Infection of H. pylori correlated with chronic and active inflammatory cellular infiltration (P < 0.001). Bile reflux did not correlate with the severity of chronic and active inflammatory cellular infiltration or H. pylori infection.Conclusions Bile reflux into the gastric remnant was observed by Bilitec 2000. Mucosal erythema and chronic, active inflammatory cell infiltration in the gastric remnant after gastrectomy may be caused by bile reflux or H. pylori infection, respectively.     

Gastric epithelial cell turnover and mucosal protection in Japanese children with Helicobacter pylori infection

Background In adults, epithelial cell proliferation and apoptosis of the gastric mucosa are induced by Helicobacter pylori infection and are associated with gastric atrophy or gastric carcinoma. In children, there are few studies about such epithelial changes. To elucidate the role of H. pylori infection in gastric mucosal inflammation, we immunohistochemically examined gastric mucosa of Japanese children.Methods Biopsy specimens obtained from the gastric antrum and corpus of H. pylori-infected (n = 13) and noninfected children (n = 15) were studied for immunolocalization of Ki-67, single-strand DNA, manganese superoxide dismutase (Mn-SOD), and CD68, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In 10 patients with successful eradication, pre- and posttreatment results were compared.Results In both gastric antrum and corpus, neutrophil and mononuclear cell infiltration, epithelial cell proliferation, and apoptosis significantly increased in H. pylori-infected patients, predominantly in the antrum. In the antrum of H. pylori-infected patients, there was positive correlation between the degrees of neutrophil infiltration and cell proliferation (P < 0.05) or apoptosis (P < 0.05). H. pylori eradication improved mucosal inflammation, cell proliferation (P < 0.001), and apoptosis (P < 0.01) in the antrum. Mn-SOD immunoreactivity and CD68-positive macrophages in the antrum, which significantly increased in H. pylori-infected patients, decreased after the eradication.Conclusions H. pylori infection induced gastric mucosal inflammation and epithelial cell turnover in children. Moreover, gastric mucosal defense mechanism against H. pylori infection was activated. H. pylori eradication in childhood might prevent the accumulation of gastric epithelial cell damage.     

Reflux esophagitis after eradication of Helicobacter pylori is associated with the degree of hiatal hernia

Background: Several studies have shown that reflux esophagitis (RE) occurs after eradication of Helicobacter pylori. However, endoscopic findings do not allow prediction of the development of RE after successful treatment. In this study, we evaluated the relationship between the prevalence of RE after eradication therapy and the degree of hiatal hernia. Methods: The study comprised 148 patients who had undergone H. pylori eradication therapy over the past 5 years. The degree of RE and hiatal hernia was evaluated based on endoscopic findings. Hiatal hernia was graded according to Hill's gastroesophageal flap valve (GEFV; grades I-IV) classification. RE after eradication therapy was graded according to the Los Angeles classification system. H. pylori infection was confirmed in all patients by culture, urease test and histological examination of antral and fundic biopsy specimens. Results: Among 148 patients, there were 122 patients (82.4%) with successful and 26 (17.6%) with failed eradication therapy. RE was diagnosed in 25 (20.5%) out of 122 patients with successful therapy but only in 1 (3.8%) out of 26 patients with failed therapy (P?&;lt;?0.05). After successful eradication, 25 patients had mild RE (12 with grade A, 13 with grade B). Among patients of the successful eradication group (n?=?122), RE was diagnosed in 2 (5.3%) out of 38 patients without hiatal hernia and in 23 (27.4%) out of 84 patients with hiatal hernia (P?=?0.0051). Furthermore, RE was diagnosed in 2 (5.3%) out of 38 patients with GEFV grade I, 13 (24.1%) out of 54 with grade II, 7 (30.4%) among 23 with grade III, and 3 (42.9%) out of 7 patients with grade IV. The pH level of gastric juice after eradication therapy was lower in the group with successful eradication than in the group with failed therapy regardless of the incidence and degree of RE. Conclusions: There is a high incidence of RE after successful H. pylori eradication therapy. This incidence of RE was closely associated with the presence and degree of hiatal hernia and with the decrease in gastric juice pH. These findings suggest that the presence of hiatal hernia together with increase in gastric acidity are important determinant factors for the development of RE after successful H. pylori eradication therapy.     

Autofluorescence imaging for predicting development of metachronous gastric cancer after Helicobacter pylori eradication

Background and Aims: Although Helicobacter pylori eradication decreases the incidence of metachronous gastric cancer after endoscopic treatment for early gastric cancer (EGC), metachronous cancer still develops after successful eradication, particularly in patients with severe corpus gastritis. We investigated whether the extent of atrophic fundic gastritis diagnosed by autofluorescence imaging (AFI) videoendoscopy is predictive of development of metachronous gastric cancer after H. pylori eradication in patients treated with endoscopic submucosal dissection (ESD) for EGC. Patients and Methods: A total of 82 patients who underwent ESD for EGC from 2003 to 2006, who received eradication therapy participated in this study. The extent of chronic atrophic fundic gastritis was evaluated by AFI and categorized into closed and open type. The main outcome was the incidence of metachronous gastric cancer detected by annual surveillance endoscopy. Results: During a median observation period of 55 months, metachronous gastric cancer developed in 12 of 82 patients (14.6%). Multivariate Cox's proportional hazard analysis revealed that open‐type, atrophic fundic gastritis diagnosed by AFI was significantly associated with development of metachronous gastric cancer (hazard ratio: 4.88, 95% confidence interval [CI]: 1.32–18.2, P = 0.018) after adjustment for age, sex, histological intestinal metaplasia, serum pepsinogen level, and H. pylori status. Conclusions: Metachronous EGC developed after successful H. pylori eradication, and extensive atrophic fundic gastritis diagnosed by AFI was a significant predictor, thus it could identify patients undergoing ESD for EGC who still required intensive surveillance after eradication.     

Relevance of VacA and mucosal pathological changes in Chinese patients with upper gastrointestinal diseases before and after Helicobacter pylori eradication

OBJECTIVE: To investigate the influence of VacA activity on gastric mucosa prior to and after Helicobacter pylori eradication in Chinese patients with peptic ulcers and chronic gastritis. METHODS: Seventy‐four dyspeptic patients with H. pylori infection were enrolled. The status of H. pylori infection was evaluated by culture and histo­pathology before and 4?6 weeks after H. pylori eradication therapy. Histological specimens were examined and graded semiquantitatively according to the updated Sydney classification. RESULTS: Helicobacter pylori with VacA was found in 59 of 74 patients (80%), and its prevalence in patients with peptic ulcers and chronic gastritis was similar. Helicobacter pylori eradication rates in patients with VacA⁺ and VacA^? strains were similar. Before eradication, the degrees of acute or chronic inflammation, epithelial damage, atrophy, intestinal metaplasia (IM) and the number of lymphoid follicles were similar in patients with VacA⁺ and VacA^?H. pylori. Four to 6 weeks after the eradication of H. pylori infection, the degrees of acute and chronic inflammation, and epithelial damage in the antrum decreased significantly, particularly in patients with VacA⁺H. pylori (P < 0.0001). The number of lymphoid follicles in the antrum also decreased more in patients with VacA⁺H. pylori than in those with VacA^?H. pylori (P= 0.051). However, there was no difference in the extent of atrophy and IM between these two groups. CONCLUSIONS: There is no specific correlation between VacA⁺/VacA^?H. pylori strains and mucosal clinicopathological features in Chinese patients with upper gastrointestinal diseases before and after eradication therapy. Successful eradication of H. pylori infection does not improve atrophic and IM lesions of the gastric mucosa.     

Relationship between interleukin-8 levels and myeloperoxidase activity in human gastric mucosa

Although interleukin (IL)-8 is well known as a chemotactic agent for neutrophil migration in vitro, the relationship between IL-8 activity and the degree of neutrophil infiltration in gastric mucosa is still unclear. In the present study, we investigated IL-8 and myeloperoxidase activity, a marker of neutrophil infiltration, in gastric antral mucosa using biopsy samples in 23 patients with no gastric lesions. The results indicate that there is a good correlation between IL-8 and myeloperoxidase activity (y = 0.173x + 13.9; r = 0.49, P<0.01). Furthermore, IL-8 and myeloperoxidase activity are significantly higher in Helicobacter pylori-positive patients than in H. pylori-negative patients. In conclusion, an increase of IL-8 activity in the gastric mucosa causes increased neutrophil infiltration in human gastric mucosa and H. pylori infection acclerates these reactions in the mucosa.     

H+/K+-adenosine triphosphatase mRNA in gastric fundic gland mucosa in patients infected with Helicobacter pylori.

BACKGROUND: How Helicobacter pylori infection affects gastric acid secretion has not been made clear. This study aimed to elucidate the effects of H. pylori infection on H+/K+-adenosine triphosphatase (ATPase) mRNA in gastric fundic gland mucosa. METHODS: Twenty patients with chronic gastritis and H. pylori infection were treated with lansoprazole and antibiotics. Before and 1 month after treatment gastroduodenoscopy was performed, and changes in the amount of H+/K+-ATPase mRNA in the fundic gland mucosa, gastric juice pH, and serum gastrin levels were determined. RESULTS: The amount of H+/ K+-ATPase mRNA in the fundic gland mucosa was increased in patients with eradication of H. pylori, in whom significant decreases in gastric juice pH and serum gastrin levels were observed. No significant changes were observed in patients without eradication of H. pylori. CONCLUSIONS: These results suggest that one of the mechanisms by which H. pylori infection suppresses acid secretion is by the inhibition of proton pump synthesis in parietal cells.     

No additive effect between Helicobacter pylori infection and portal hypertensive gastropathy on inducible nitric oxide synthase expression in gastric mucosa of cirrhotic patients

Increased expression of inducible nitric oxide synthase (iNOS) has been reported in gastric mucosa of patients with Helicobacter pylori infection or portal hypertensive gastropathy (PHG) but whether there is an additive or synergistic impact between H. pylori and PHG on iNOS expression was unknown. Sixty cirrhotic patients and 21 age-matched control subjects without liver disease were included. Biopsies from the gastric antrum and body were obtained for quantitative histological assessment and immunohistochemical staining for iNOS. iNOS staining was detected in endothelial cells and macrophages. In the absence of PHG, H. pylori significantly induced iNOS expression in cirrhotic patients. PHG also significantly induced iNOS expression in H. pylori-negative patients. However, there was no synergistic or additive effect between H. pylori and PHG on this expression. Furthermore, expression of iNOS was significantly higher in patients with severe PHG than in those with mild PHG and without PHG.     

The expression level of TRAF1 in human gastric mucosa is related to virulence genotypes of Helicobacter pylori

Abstract

Objective. To investigate the expression level of tumor necrosis factor receptor-associated factor 1 (TRAF1) in gastric mucosa tissue in patients infected with Helicobacter pylori (H. pylori) and to analyze the relationship between TRAF1 expression and H. pylori virulence. Methods. Gastric tissue samples were collected from patients with gastritis, atrophic gastritis, intestinal metaplasia with atypical hyperplasia, and gastric cancer. The expression level of TRAF1 in each group was analyzed by real-time polymerase chain reaction (PCR) and Western blot analysis. Virulence genotypes of H. pylori were determined by PCR. Results. Significant differences in TRAF1 mRNA levels were observed between the gastritis and gastric cancer groups, and the atrophic gastritis and gastric cancer groups (p < 0.05). Moreover, significant differences in TRAF1 protein levels were observed between the gastritis and intestinal metaplasia with atypical hyperplasia groups, between the gastritis and gastric cancer groups, and between the atrophic gastritis and gastric cancer groups (all p < 0.05). The virulence genotypes of cytotoxin-associated gene A (cagA), vacAs1, and vacAm1 were more frequent in the TRAF1 high-level group than in the TRAF1 low-level group (p < 0.05). Conclusion. Higher TARF1 expression level is associated with infection by CagA⁺/vacAs1⁺/m1⁺ virulent H. pylori strains and may promote the proliferation of gastric mucosal cells and induce gastric cancer.     

Analysis of factors associated with recovery of the serum pepsinogen ratio after Helicobacter pylori eradication: a long-term follow-up study in Korea

Abstract

Objective: Serum levels of pepsinogen (PG) are related to Helicobacter pylori-induced inflammation of the gastric mucosa. This study aimed to examine the influence of H. pylori eradication on serum PG, analyze its associated factors, and evaluate the long-term outcomes.

Methods: H. pylori-positive patients who underwent gastroscopy and serum PG measurement were enrolled in a single academic hospital. After H. pylori eradication, the measurement of serum PG level was performed. Recovery of serum PG I/II ratio was defined as a PG I/II ratio after eradication of >3.0 in patients with a PG I/II ratio ≤ 3.0 before eradication. Follow-up involved serum PG measurement and gastroscopy with a rapid urease test annually.

Results: In all, 327 patients were eligible for study inclusion. Compared to those before H. pylori eradication, serum PG I (74.9 vs. 44.3?ng/mL, p?<?.001) and PG II (25.4 vs. 9.1?ng/mL, p?<?.001) levels significantly decreased after successful eradication. In addition, there was a significant increase in serum PG I/II ratio after eradication (3.07 vs. 4.98, p?<?.001). In multivariate analyses, the following were independently associated with failed recovery of serum PG I/II ratio despite successful eradication: age ≥ 60?years (odds ratio [OR]?=?0.231, 95% confidence interval [CI]?=?0.084–0.629, p?=?.004) and severe gastric atrophy (OR = 0.156, 95% CI = 0.055–0.440, p?<?.001).

Conclusions: Recovery of serum PG I/II ratio after H. pylori eradication may be achieved in H. pylori-infected patients aged <60?years without severe gastric atrophy.     

Histological characteristics of gastric mucosa prior to Helicobacter pylori eradication may predict gastric cancer

Abstract

Objective. Although Helicobacter pylori (H. pylori) eradication has been shown to inhibit gastric cancer, it does not completely suppress it. Therefore, risk factors of gastric cancer development following H. pylori eradication were examined. Material and methods. A total of 2355 patients (1501 males and 824 females) underwent successful eradication of H. pylori. Endoscopic atrophy, histological gastritis, atrophy, intestinal metaplasia (IM), and operative link for gastritis assessment (OLGA) staging were subsequently evaluated. Results. Following eradication, 33/2355 patients (25 males and 8 females) developed gastric cancer. Compared to a nongastric cancer group that was matched according to gender and age, the incidence of endoscopic atrophy (3.52 ± 1.45 vs. 4.85 ± 1.18, p < 0.001), histological atrophy at the greater curvature of the antrum (1.42 ± 0.80 vs. 1.95 ± 0.86, p = 0.0059), inflammation (2.05 ± 0.59 vs. 2.33 ± 0.66, p = 0.031), IM at the greater curvature of the corpus (0.06 ± 0.30 vs. 0.24 ± 0.54, p = 0.029), the ratio of OLGA-stage 0–II/III, IV (13/8 vs. 55/11, p = 0.038) were significantly higher for the gastric cancer group. Multivariate analysis also showed the highest odds ratio (6.26, 95% confidence interval or CI, 1.28–30.60, p = 0.023) for IM at the greater curvature of the corpus. Conclusions. Severe endoscopical atrophy, OLGA staging, histological atrophy at the antrum, inflammation, and particularly IM at the corpus, were identified as risk factors for gastric cancer development following H. pylori eradication. Therefore, eradication should be performed before these predictors develop.     

Helicobacter pylori Infection Influences Tumor Growth of Human Gastric Carcinomas

Background: Helicobacter pylori infection is considered a risk factor for gastric carcinoma. However, the effect of eradication therapy in gastric carcinoma patients is not well known. The aim of this study was to investigate the relationship between H. pylori infection and tumor growth of gastric carcinoma. Methods: Fifty-one patients with gastric carcinoma participated in the study. Thirty-three were H. pylori-positive, 6 were H. pylori-negative, and 12 were diagnosed with gastric carcinoma after eradication of H. pylori. To investigate tumor growth of gastric carcinoma, cell proliferation and angiogenesis of the tumors were evaluated by immunohistochemical techniques using Ki-67 and CD34. Results: The Ki-67 labeling index was 47.9?±?2.6 (mean?±?s) in the H. pylori-positive group, 38.1?±?3.6 in the H. pylori-eradicated group, and 22.2?±?5.5 in the H. pylori-negative group. It was significantly lower in the H. pylori-eradicated and H. pylori-negative groups than in the H. pylori-positive one, and a significant difference was also found between the H. pylori-positive and H. pylori-eradicated groups. The microvessel counts were 62.5?±?3.0, 50.2?±?4.0, and 66.0?±?9.8 in the positive, eradicated, and negative groups, respectively. A significant difference was found between the H. pylori-positive and H. pylori-eradicated groups. Conclusion: Our results suggest that H. pylori infection is associated with cell proliferation, and its eradication may influence tumor vascularity of gastric carcinoma. Therefore, H. pylori eradication therapy may contribute to the suppression of tumor growth.     

Helicobacter pylori stimulates inducible nitric oxide synthase in diverse topographical patterns in various gastroduodenal disorders

Overproduction of nitric oxide by inducible nitric oxide synthase (iNOS) acts cytotoxically and contributes to inflammation. We explored the roles of iNOS in the pathogenesis of Helicobacter pylori-associated diseases. Using reverse-transcribed PCR, we examined topographical patterns of iNOS mRNA expression in the gastroduodenal mucosa in H. pylori-negative controls and H. pylori-positive patients with duodenal ulcer (DU), gastric ulcer (GU), and ulcer-free gastritis. iNOS expression showed topographical variations among the tested disorders. As compared to controls, DU had a significantly higher expression of iNOS mRNA in the duodenum, GU in the antrum and duodenum, and gastritis in the antrum and corpus. H. pylori eradication yielded a significant reduction of iNOS mRNA in the duodenum of DU and in the antrum of GU. Diverse topographical patterns of H. pylori-induced iNOS expression may contribute to mechanisms by which H. pylori elicits different clinical disorders.     

Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa

Background and Aim: Gene silence of IRX1 tumor suppressor by promoter CpG methylation combined with loss of heterozygosity (LOH) has been identified in human gastric cancer. This study investigated the association between methylation of IRX1 and Helicobacter pylori infection in gastric mucosa tissues and cell line. Methods: IRX1 methylation was studied by methylation specific polymerase chain reaction (MSP) and bisulfate sequencing polymerase chain reaction (BSP) methods in gastric mucosa tissues from H. pylori‐positive chronic gastritis patients or H. pylori‐negative chronic gastritis patients. Promoter activity, methylation status and gene expressing level of IRX1 were evaluated by persistent infecting H. pylori on human gastric cells GES‐1 in vitro. Electron microscopy was used to observe the effect of H. pylori infection on GES‐1 gastric mucosa cells. Results: The methylation level of IRX1 promoter in H. pylori positive chronic gastritis and H. pylori negative chronic gastritis was 55.30% ± 13.17 versus 5.20% ± 6.31, respectively (P < 0.01). H. pylori infection stimulated increased microvillus, and mucous secretion on GES‐1 cells. Infection of H. pylori induced IRX1 promoter methylation and downregulation of the promoter activity as well as gene expression significantly. Conclusions: This study firstly demonstrated that H. pylori infection contributes to IRX1 promoter methylation on gastric mucosa.