Apoptosis in chronic gastritis and its correlation with antigastric autoantibodies

 In the course of time, chronic gastritis may result in gastric atrophy, as in type A gastritis, where autoimmune reactions against parietal cells result in a loss of corpus glands. Two antigastric autoantibodies have been detected in Helicobacter pylori gastritis and are described as anti-luminal and anti-canalicular autoantibodies. The aim of this study was to determine whether increased apoptosis may be responsible for the loss of gastric epithelium and whether this apoptosis is correlated with antigastric autoimmunity. Gastric biopsies from normal mucosa and Helicobacter pylori gastritis were analysed for the presence of apoptosis using the TUNEL method. Helicobacter pylori gastritis was divided into cases (1) without autoantibodies, (2) with anti-luminal, and (3) with anti-canalicular autoantibodies. Apoptotic cells of the foveolar and of the glandular epithelium in the antrum and corpus were counted. The number of apoptotic cells in the gastric mucosa was significantly increased in all cases of gastritis. The highest number of apoptotic cells was observed in the gastric glands of the corpus mucosa in Helicobacter pylori gastritis with anti-canalicular autoantibodies. Apoptosis contributes to the development of gastric atrophy and there are various types of Helicobacter pylori gastritis. The positive correlation between apoptotic cell loss in the glandular zone of the corpus mucosa and the presence of anti-canalicular autoantibodies indicates a possible link between antigastric autoimmunity and atrophy in this type of Helicobacter pylori gastritis – similar to that in classic type A gastritis. Received: 19 November 1997 / Accepted: 24 March 1998     

The Story So Far: Helicobacter Pylori and Gastric Autoimmunity

The gastric mucosal pathogen Helicobacter pylori induces autoantibodies directed against the gastric proton pump H⁺,K⁺-ATPase in 20–30% of infected patients. The presence of these autoantibodies is associated with severity of gastritis, increased atrophy, and apoptosis in the corpus mucosa, and patients with these autoantibodies infected with H. pylori display histopathological and clinical features that are similar to those of autoimmune gastritis (AIG). This review will focus on the T helper cell responses, cytokines, and adhesion molecules involved in corpus mucosal atrophy in chronic H. pylori gastritis and in AIG, and the role of H. pylori in the onset of AIG.     

Interleukin-6 polymorphism and Helicobacter pylori infection in Brazilian adult patients with chronic gastritis

Abstract Helicobacter pylori is recognised as the most common cause of chronic active gastritis and this bacterium is also an important pathogenic factor in peptic ulcer disease. The biological factors that influence clinical outcome in H. pylori infection have been extensively studied. In addition to immunological factors in the host, bacterial virulence determinants in H. pylori strains are likely to play a crucial role in gastric cancer development. Singlenucleotide polymorphisms at the 5' flanking region of the interleukin (IL)-6 gene promoter (G or C at -174 base) have been identified and individuals with the G allele at position -174 have been shown to produce higher levels of IL-6 than those with the C/C genotype. The mucosal levels of IL-6 were reported to be increased in H. pylori-associated gastritis. The present study was conducted to examine any relationship between inflammatory cytokine polymorphisms and the inflammatory process in mucosa infected by H. pylori. In our study we did not find any association between the C and G alleles in adult patients with chronic gastritis and inflammatory process in gastric mucosa.     

Implications for a role of interleukin‐23 in the pathogenesis of chronic gastritis and of peptic ulcer disease

The present study aimed to investigate the role of gastric mucosa for the secretion of interleukin (IL)‐23 in chronic gastritis. One hundred and one patients were enrolled; 47 with duodenal ulcer, 33 with gastric ulcer and 31 with chronic gastritis. Biopsies were incubated in the absence/presence of endotoxins. Supernatants were collected and IL‐23 and IL‐1β were measured by enzyme‐linked immunosorbent assay. Scoring of gastritis was performed according to the updated Sydney score. Patients with duodenal and gastric ulcer and those with chronic gastritis had similar scores of gastritis. IL‐23 was higher in supernatants of tissue samples of Helicobacter pylori‐positive than of H. pylori‐negative patients. No differences were recorded in concentrations of IL‐23 and IL‐1β between patients with duodenal ulcer, gastric ulcer and chronic gastritis. Positive correlations were found between IL‐23 of patients with both duodenal and gastric ulcer and chronic gastritis and the degree of infiltration of neutrophils and monocytes. Similar correlations were observed between IL‐23 and IL‐1β. IL‐23 secreted by the gastric mucosa could be implicated in the pathogenesis of chronic gastritis. IL‐23 was released in the presence of H. pylori from the inflamed gastric mucosa and followed the kinetics of IL‐1β.     

Prevalence of Helicobacter pylori infection, chronic gastritis, and intestinal metaplasia in Mozambican dyspeptic patients

We estimated the prevalence of Helicobacter pylori infection, chronic gastritis, atrophy, and intestinal metaplasia in dyspeptic patients from Maputo Central Hospital, Mozambique and evaluated the relationship between infection and histopathological features of chronic gastritis. Biopsies from 109 consecutive patients observed in 2005–2006 were collected from antrum, incisura angularis, and corpus for histopathological study according to the Modified Sydney system. H. pylori infection was assessed by histology and polymerase chain reaction. H. pylori prevalence was 94.5%. Chronic gastritis was the most frequent diagnosis (90.8%). Degenerative surface epithelial damage was associated with higher H. pylori density. Glandular atrophy (8.3%) and intestinal metaplasia (8.3%) were infrequent. Our results confirm previous observations in African countries with high prevalence of H. pylori infection and low rates of gastric cancer: high frequency of chronic H. pylori-associated gastritis with very low frequency of gastric atrophy and intestinal metaplasia.     

Helicobacter pylori and cagA and vacA gene status in children from Brazil with chronic gastritis

Abstract. Helicobacter pylori has been shown to be strongly associated with chronic gastritis, gastric and duodenal ulceration, and is a risk factor for gastric carcinoma. Histology, urease, culture, and polymerase chain reaction have been employed as for H. pylori diagnostic methods, pre and post treatment or during follow-up of dyspeptic adult individuals referred for endoscopy. In order to obtain a more-sensitive and specific method for H. pylori detection, we evaluated gastric body and antrum biopsies of 134 consecutive Brazilian consecutive dyspeptic children aged 1–16 years by rapid urease test, histology and polymerase chain reaction using two pairs of oligonucleotides. Our results indicated that polymerase chain reaction with Southern blotting and hybridization with specific chemiluminescent probes increased the number of positive H. pylori patients by 35%. The genotyping of H. pylori strains directly from gastric biopsy using the same nucleic acid methodology revealed that there is no association of chronic gastritis in our infant patients with vacA s1 and the presence of the cagA gene. These data suggest an initial infection of children with normal mucosa and probably others factors than vacA s1 genotype or the presence of the cagA gene are associated with the onset of gastric disease. Altogether, our results reinforce the need for using more sensitive diagnostic methods in order to understand the role of H. pylori in the genesis of gastric disease in children and its progression in adults.     

Light Microscopic and Ultrastructural Evidence of in Vivo Phagocytosis of Helicobacter pylori by Neutrophils

Helicobacter pylori is believed to cause chronic active gastritis. Infection/colonization of the gastric mucosal surface induces a mucosal inflammatory reaction in the form of lymphocytic aggregates, plasma cells and, particularly, neutrophils, which may, in turn, damage the mucosal epithelium. In vitro studies demonstrate that, in culture, the bacilli are readily phagocytosed by neutrophils, this evoking a neutrophilic oxidative burst. However, it has been claimed that neutrophils do not phagocytose H. pylori in vivo. In this study of 19 endoscopic biopsies of gastric mucosa with H. pylori -associated gastritis, Cresyl violet staining for light microscopy and electron microscopy areusedto demonstrate that, in vivo, neutrophils actively phagocytose and destroy the bacilli in the epithelial intercellular space and in the mucin on the surface of the mucosa. Direct contact of neutrophils with H. pylori was observed in 17 of 17 cases by light microscopy and in 4 of 15 cases by electron microscopy. Phagocytosis by neutrophils was seen in 14 of 17 cases by light microscopy and in 3 of 15 cases by electron microscopy. It was most evident in the surface mucus coat where ``wolf packs'' of neutrophils were seen attacking the microbes. Ultrastructurally, neutrophil phagolysosomes contained both intact and partially digested bacteria,convincing evidence that the primary function of neutrophils in chronic active gastritis is to destroy H. pylori organisms. This study leaves open the question of whether, or how, neutrophils damage the gastric mucosa.     

Contribution Of Epidemiological Studies To Gastritis Immunology

Chronic gastritis, or chronic inflammation in gastric antral and/or corpus mucosa, is a common pathological condition affecting over half the general population. Progression of chronic gastritis from Helicobacter pylori infection to severe gastric mucosal atrophy usually takes decades and varies considerably from person to person. Therefore, studies of clinically selected material cannot provide a complete picture of natural evolution of the disease or its wide variability. An overview of immunological and morphological aspects of chronic gastritis in an epidemiological context, based on data from the literature and the author's studies, reveal dynamic interaction between H. pylori infection and host response to the organism's antigens, and to gastric autoantigens including gastric H⁺K⁺ ATPase. Further population and followup studies of antral and corpus gastritis at different stages of evolution are needed, in combination with new methods, to elucidate further the roles of infection, and gastric-antrum- and corpus-mucosa-related autoimmune responses, in the pathogenesis of chronic gastritis.     

Helicobacter colonization and histopathological profile of chronic gastritis in patients with or without dyspepsia,mucosal erosion and peptic ulcer: A morphological approach to the study of ulcerogenesis in man

Summary Helicobacter pylori colonization and the incidence, severity, activity and topography of gastritis were investigated systematically in antrum and corpus mucosal biopsies of 1177 subjects undergoing endoscopy in the absence of gastric complaints (asymptomatic, 49) or for non-ulcer dyspepsia (NUD; 631 patients, 72 of whom had gastric and/or duodenal erosions), active gastric ulcer (GU, 76 patients), active duodenal ulcer (DU, 138 patients), and healed gastric (HGU, 39 cases) or duodenal ulcer (HDU, 230 cases). In the antrum,H. pylori colonization and the incidence, severity and activity of gastritis increased progressively in the sequence asymptomatic, erosion-free NUD, erosive NUD, healed ulcer and active ulcer. The same trend was observed in the corpus as regardsH. pylori and gastritis incidence, whereas the severity and activity of gastritis were lower in active DU and erosive NUD and higher in active, proximal GU than in the remaining patients. Active DU and erosive NUD showed the highest incidence of nonatrophic gastritis and lowest type-A or AB atrophic gastritis, while active GU had lowest normal mucosa or type-A gastritis and highest type-B atrophic gastritis. In conclusion,H. pylori colonization and gastritis incidence, severity and, especially, activity of the antrum might all contribute to mucosal erosion and ulceration, whereas the same factors, at least in part and with the exception of proximal GU, seem to have a preventive role when affecting corpus mucosa.     

An unusual presentation of <Emphasis Type="Italic">helicobacter pylori</Emphasis> infection: so-called “Russell body gastritis”

Helicobacter pylori (H. pylori) is a slow bacterial pathogen, which induces several gastroduodenal diseases. Varying degrees of inflammation can be present in the gastric mucosa of patients infected with H. pylori. The case presented here is a male patient suffering from dyspepsia and nausea. His upper gastrointestinal endoscopy revealed pan gastritis. Histological examination of multiple gastric biopsies taken from the body and antrum showed a rare morphological expression of H. pylori gastritis characterized by diffuse plasma cell infiltration with extensive Russell body formation. Diffuse infiltration of plasma cells with Russell bodies in gastric mucosa can cause difficulties in differentiation from neoplastic processes. However, immunohistochemically, the infiltrating cells in the gastric mucosa stained negatively with cytokeratins while they expressed both kappa and lambda light chains showing their polyclonal nature. The presence of diffuse plasma cells with Russell bodies in the gastric mucosa may represent a different presentation of H. pylori gastritis. There are only two case reports of similar presentation and both have been called Russell body gastritis.     

Increased expression and cellular localization of lipocalin‐type prostaglandin D synthase in Helicobacter pylori‐induced gastritis

Immunological responses in the host can result in different disease outcomes of Helicobacter pylori‐induced gastritis. Prostaglandin E2 derived from cyclooxygenase (COX) and prostaglandin E synthase contribute to gastric protection. Recently, prostaglandin D2 was shown to be involved in host immunity by chemotactic activity through chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTH2), but its role in H. pylori‐induced gastritis has not been clarified. We determined the expression levels of mRNAs for haematopoietic PGD synthase (H‐PGDS) and lipocalin‐type PGDS (L‐PGDS), MIP‐1 alpha, IFN‐gamma, IL‐4, and CDX2 in H. pylori‐induced gastritis mucosa by quantitative RT‐PCR. We found that L‐PGDS was constitutively expressed in the epithelium of the glandular base. L‐PGDS, but not H‐PGDS, was induced on fibroblasts close to infiltrating cells in the H. pylori‐infected gastric mucosa. These fibroblasts co‐expressed COX‐2. The level of L‐PGDS mRNA expression decreased as gastritis became more severe. In most of the H. pylori‐infected gastric mucosa, CCR5(+) cells had more actively infiltrated than had CRTH2(+) cells. However, the expression level of IFN‐gamma was lower in the mucosa of the CRTH2(+) cells‐dominantly infiltrating group than that of the less CRTH2‐infiltrating group. Exogenously added PGD2 decreased the H. pylori‐induced expression of IFN‐gamma in peripheral blood mononuclear cells in vitro. The data suggest that PGD2 derived from the gastric mucosa and fibroblasts plays protective roles against inflammatory changes in H. pylori‐induced gastritis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis>-infection-associated CpG island hypermethylation in the stomach and its possible association with Polycomb repressive marks

Helicobacter pylori infection can induce CpG island (CGI) hypermethylation in gastric mucosa. Recently, genes occupied by Polycomb proteins in embryonic stem cells were shown to be vulnerable to aberrant DNA hypermethylation in cancers. To explore the relationship between H. pylori infection and DNA methylation changes in neoplastic and non-neoplastic stomach, we analyzed 25 CGIs and repetitive DNA elements from 82 chronic gastritis and 69 gastric carcinomas. Twenty-three CGIs showed significantly higher methylation levels in H. pylori-negative gastric carcinoma (n = 28) than in H. pylori-negative chronic gastritis (n = 39; P < 0.05), indicating cancer-associated methylation. Eight CGIs exhibited significantly higher methylation levels in H. pylori-positive chronic gastritis (n = 43) than in H. pylori-negative chronic gastritis (n = 39; P < 0.05). Six CGIs showed both cancer-associated and H. pylori-associated hypermethylation. Six (75%) of the eight H. pylori-associated hypermethylated genes contained at least one of three repressive marks (Suz12 occupancy, Eed occupancy, histone H3 K27 trimethylation), whereas 31% of the remaining cancer-associated hypermethylated genes had at least one mark. The findings suggest that H. pylori infection strongly induces CGI hypermethylation in gastric epithelial cells and that susceptibility to H. pylori-induced DNA hypermethylation may be determined by Polycomb repressive marks in stem or progenitor cells. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Supported by the Korea Research Foundation Grant (MOEHRD; KRF-2005-041-E00081; G.H.K.) and by the second stage Brain Korea 21 Project.     

Simultaneous gastric adenocarcinoma and MALT-type lymphoma in Helicobacter pylori infection

A 79-year-old women with upper abdominal pain, vomiting and weight loss was found at endoscopy to have a large tumour mass in the gastric body. Histology of forceps biopsies revealed an adenocarcinoma of intestinal type. Gastrectomy was performed, but extensive lymph node metastasis precluded a curative surgical approach. Histopathological study of the specimen, however, revealed two distict malignancies, which arose in the setting of Helicobacter pylori-associated chronic gastritis with partial mucosal atrophy. One tumour was a gastric carcinoma, while the other was a primary B-cell lymphoma of the stomach (CD20-positive). The lymphoma comprised both a low-grade component (mucosa-associated lymphoid tissue- or MALT-type lymphoma), and a high-grade component (large cell lymphoma with CD30-positive giant cells). Infection with H. pylori was confirmed by the serological presence of IgG antibodies to H. pylori-antigens, including antibodies against the 128 kDa protein of the cytotoxin-associated gene (cagA gene) of H. pylori.     

Helicobacter pylori regulates TLR4 and TLR9 during gastric carcinogenesis

Objective: To investigated the influence of H. pylori on TLR4 and TLR9 in gastric mucosa during gastric carcinogenesis. Methods: Gastric biopsy specimens were taken from 148 patients and divided into five groups, including normal group (n = 10), chronic superficial gastritis group (n = 35), atrophy/intestinal metaplasia group (n = 35), dysplasia group (n = 34) and gastric carcinoma group (n = 34). Immunohistochemistry was used to detect the expression of TLR4 and TLR9. Geimsa staining and rapid urea test were used for determine H. pylori infection. Results: TLR4 was detected in gastric epithelium and monocytes/macrophages in superficial gastritis, atrophy/intestinal metaplasia, dysplasia or carcinoma. TLR9 was mainly accentuated in monocytes/macrophages. TLR4 positive cells in epithelium and in monocytes/macrophages with H. pylori infection were much more than those without H. pylori infection. Similar results were also found in TLR9. When gastric epithelium was accompanied with H. pylori infection, TLR4 was significant higher in superficial gastritis and atrophy/intestinal metaplasia groups compared with dysplasia and carcinoma groups. When gastric epithelium was infected by H. pylori, TLR9 was significant higher in carcinoma group compared with superficial gastritis, atrophy/intestinal metaplasia and dysplasia. TLR4 and TLR9 show significant correlation with the severity of inflammation. Conclusions: H. pylori infection was associated with increased expression of TLR4 and TLR9 in gastric mucosa. In superficial gastritis and atrophy/intestinal metaplasia the inflammation was predominately mediated by TLR4, while in gastric cancer the inflammation was mainly mediated by TLR9.     

Treatment of Helicobacter pylori infection in mice with oral administration of egg yolk-driven anti-UreC immunoglobulin

Background

Helicobacter pylori, the causative agent of gastritis and gastric ulcer, plays a crucial role in development of gastric carcinomas. Antibiotic therapy fails in almost 20% of cases due to development of antibiotic resistance. Development of antibodies against specific H. pylori targets could have significant therapeutic effect. In the present research attempts have been made to study the effect of IgY purified from egg yolk of hens immunized with recombinant UreC in treatment of mice infected with H. pylori.

Materials and methods

Purified IgY-HpUc was used in two forms: powdered and PBS dissolved. 10⁹ bacteria in BHI were orally administered to C57BL6/j mice three times on alternate day intervals. Eight weeks after the last inoculation, the serum was assayed for infection rate by ELISA. The severity of gastritis was analyzed histopathologically. Infected mice were randomly divided into three groups. Groups one and two were treated with dietary IgY-HpUc and IgY-HpUc dissolved in PBS respectively for 28 days. The untreated group served as control.

Results

Serology and histopathology confirmed the establishment of the infection. Indirect ELISA results in the treated animals showed considerable reduction of H. pylori specific antibodies in their sera. Pathological examination of gastric mucosa of infected mice treated with IgY-HpUc showed considerable reduction of inflammation in the stomach tissues. The bacterial presence on mucosal layer of the stomach was considerably reduced.

Conclusions

UreC-induced IgY is specifically successful in inhibition of H. pylori infection and could be an alternative to antibiotic treatment.     

Characterization of progressive metaplasia in the gastric corpus mucosa of Mongolian gerbils infected with Helicobacter pylori

Spasmolytic polypeptide‐expressing metaplasia (SPEM) and intestinal metaplasia are considered neoplastic precursors of gastric adenocarcinoma in humans. Loss of parietal cells causes the development of SPEM in the gastric corpus and then chronic inflammation drives SPEM toward a more proliferative lineage. Mongolian gerbils infected with Helicobacter pylori develop chronic gastritis and metaplasia, mimicking aspects of human gastritis with H. pylori infection. We therefore examined metaplastic lineages in the gastric corpus mucosa of gerbils infected by H. pylori strain 7.13, which produces rapid onset of severe inflammation. Six weeks following H. pylori infection, Griffonia simplicifolia lectin II (GSII)‐positive SPEM developed in the base of oxyntic glands in association with parietal cell loss and inflammation. In association with severe inflammation, SPEM glands evolved into aberrant phenotypes, including branched lesions, dilated lesions, and penetrating invasive glands. Mucin 4 (MUC4) was up‐regulated in SPEM and progressive SPEM. Clusterin was expressed in the tips of branched and dilated lesions and throughout regions of invasive glands. Intriguingly, clusterin‐positive regions in these lesions expressed Ki67 and matrix metalloproteinase 7 (MMP‐7). These same regions were also positive for expression of phospho‐IkBα, suggestive of activated NFkB signalling. These findings suggest that clusterin‐positive regions in progressive phenotypes of SPEM have invasive characteristics. Thus, H. pylori infection in gerbils induces SPEM, which then can progress to further aberrant and invasive metaplastic phenotypes. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology

Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, leading to chronic gastritis, peptic ulcers, gastric carcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Recent studies have shown that apoptosis of gastric epithelial cells is increased during H. pylori infection. Apoptosis induced by microbial infections are factors implicated in the pathogenesis of H. pylori infection. The enhanced gastric epithelial cell apoptosis in H. pylori infection has been suggested to play an important role in the pathogenesis of chronic gastritis and gastric pathology. In addition to directly triggering apoptosis, H. pylori induces sensitivity to tumor-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in gastric epithelial cells via modulation of TRAIL apoptosis signaling. Moreover, H. pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis. In H. pylori infection, there was significantly increased CCR6⁺CD3⁺ T-cell infiltration in the gastric mucosa, and the CCR6 ligand, CCL20 chemokine, was selectively expressed in inflamed gastric tissues. These results implicate that the interaction between CCL20 and CCR6 may play a role in recruiting T cells to the sites of inflammation in the gastric mucosa during Helicobacter infection. Through these mechanisms, chemokine-mediated T lymphocyte trafficking into inflamed epithelium is initiated and the mucosal injury in Helicobacter infection is induced. This article will review the recent novel findings on the interactions of H. pylori with diverse host epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation, mucosal damage and development of MALT lymphomas.     

The number of Foxp3-positive regulatory T cells is increased in Helicobacter pylori gastritis and gastric cancer

Helicobacter pylori (H. pylori) colonization induces vigorous innate and specific immune responses; however, the infection is not removed, a state of chronic active gastritis persists for life if untreated. Recent studies have shown that CD4⁺ CD25⁺ Foxp3-positive regulatory T cells (Tregs) suppress the immune response to H. pylori. Persistent H. pylori-associated gastritis is closely associated with gastric carcinogenesis. We investigated the number of Tregs in the context of H. pylori colonization in chronic gastritis, examined the relationship between it and histopathological findings and compared it with that of gastric dysplasia and adenocarcinoma. This study was based on the analysis of gastric biopsy specimens from 126 cases of H. pylori-associated gastritis, 16 cases of H. pylori-negative gastritis, 17 cases of gastric dysplasia, and 25 cases of gastric adenocarcinoma. The number of Tregs was elevated in H. pylori-associated gastritis, where it was positively correlated with the grade of chronic inflammation and the number of lymphoid follicles. It was significantly elevated in adenocarcinomas compared to chronic gastritis and gastric dysplasia. In summary, the number of Tregs is increased in H. pylori-associated gastritis and gastric cancer.     

Role of Interleukin-32 in Helicobacter pylori-Induced Gastric Inflammation

Helicobacter pylori infection is associated with gastritis and gastric cancer. An H. pylori virulence factor, the cag pathogenicity island (PAI), is related to host cell cytokine induction and gastric inflammation. Since elucidation of the mechanisms of inflammation is important for therapy, the associations between cytokines and inflammatory diseases have been investigated vigorously. Levels of interleukin-32 (IL-32), a recently described inflammatory cytokine, are increased in various inflammatory diseases, such as rheumatoid arthritis and Crohn''s disease, and in malignancies, including gastric cancer. In this report, we examined IL-32 expression in human gastric disease. We also investigated the function of IL-32 in activation of the inflammatory cytokines in gastritis. IL-32 expression paralleled human gastric tissue pathology, with low IL-32 expression in H. pylori-uninfected gastric mucosa and higher expression levels in gastritis and gastric cancer tissues. H. pylori infection increased IL-32 expression in human gastric epithelial cell lines. H. pylori-induced IL-32 expression was dependent on the bacterial cagPAI genes and on activation of nuclear factor κB (NF-κB). IL-32 expression induced by H. pylori was not detected in the supernatant of AGS cells but was found in the cytosol. Expression of the H. pylori-induced cytokines CXCL1, CXCL2, and IL-8 was decreased in IL-32-knockdown AGS cell lines compared to a control AGS cell line. We also found that NF-κB activation was decreased in H. pylori-infected IL-32-knockdown cells. These results suggest that IL-32 has important functions in the regulation of cytokine expression in H. pylori-infected gastric mucosa.     

Helicobacter pylori: Bacterial Strategy for Incipient Stage and Persistent Colonization in Human Gastric Niches

Helicobacter pylori (H. pylori) undergoes decades long colonization of the gastric mucosa of half the population in the world to produce acute and chronic gastritis at the beginning of infection, progressing to more severe disorders, including peptic ulcer disease and gastric cancer. Prolonged carriage of H. pylori is the most crucial factor for the pathogenesis of gastric maladies. Bacterial persistence in the gastric mucosa depends on bacterial factors as well as host factors. Herein, the host and bacterial components responsible for the incipient stages of H. pylori infection are reviewed and discussed. Bacterial adhesion and adaptation is presented to explain the persistence of H. pylori colonization in the gastric mucosa, in which bacterial evasion of host defense systems and genomic diversity are included.