<Emphasis Type="Italic">Helicobacter pylori</Emphasis>-secreting protein Tipα is a potent inducer of chemokine gene expressions in stomach cancer cells

Purpose Stomach cancer has a high mortality rate in East Asia, and is strongly associated with Helicobacter pylori (H. pylori) infection. H. pylori is known to express chemokine genes in the gastric mucosa, chemokines that are important host immune factors facilitating inflammation and tumor growth. To investigate the mechanism of carcinogenesis in the stomach, it is essential to determine which molecule of H. pylori is involved in induction of chemokines, but this has remained unclear. We previously reported that a tumor necrosis factor-α (TNF-α) inducing protein (Tipα) secreted from H. pylori acts as a tumor promoter in stomach cancer development, and thus started to investigate whether Tipα is involved in induction of chemokine genes. Methods Comprehensive gene expression analysis was conducted using DNA microarray and KeyMolnet analyses. The gene expression was quantitatively analyzed by real-time RT-PCR. Results Comprehensive and quantitative gene expression analyses revealed that Tipα induces gene expression of the chemokines Ccl2, Ccl7, Ccl20, Cxcl1, Cxcl2, Cxcl5 and Cxcl10 extensively and simultaneously in mouse stomach cancer cells, MGT-40. Tipα induced high levels of chemokine gene expression, whereas inactive deleted Tipα, del-Tipα, showed only marginal expression, suggesting a correlation between tumor promotion and chemokine gene expression by Tipα. MG-132, a proteasome inhibitor which represses NF-κB-activation, inhibited chemokine gene expressions. Conclusion We report here that Tipα of H. pylori gene product is a strong inducer of chemokine gene expressions, providing a new model for stomach cancer development.     

Nucleolin as cell surface receptor for tumor necrosis factor-α inducing protein: a carcinogenic factor of Helicobacter pylori

Purpose  

Tumor necrosis factor-α inducing protein (Tipα) is a unique carcinogenic factor released from Helicobacter pylori (H. pylori). Tipα specifically binds to cells and is incorporated into cytosol and nucleus, where it strongly induces expression of TNF-α and chemokine genes mediated through NF-κB activation, resulting in tumor development. To elucidate mechanism of action of Tipα, we studied a binding protein of Tipα in gastric epithelial cells.     

Expression of NF-κB in Helicobacter pylori Infection

Helicobacter pylori colonizes the gastric mucosa in humans and causes chronic gastritis. NF-κB has a key role as a mediator in mucosal inflammation. In this study, we examined the expression of NF-κB in the antral epithelial cells of H. pylori-infected and H. pylori-uninfected biopsies and examined these processes in relationship with grade and activity of gastritis, density of H. pylori, presence of the intestinal metaplasia, and atrophy. Fifty biopsies (35 H. pylori-positive patients and 15 H. pylori-negative controls) were studied. NF-κB immunohistochemical stain was performed. NF-κB activity in H. pylori-infected biopsies were markedly enhanced compared with uninflamed biopsies (P = 0.001). We also found positive correlation NF-κB expression with severity of gastritis (according to Sydney score) (P = 0.001), activity of gastritis (P = 0.046) and H. pylori load (P < 0.001), and atrophy (P = 0.004). We did not find a significant relationship between NF-κB and the presence of intestinal metaplasia (P = 0.355). These findings suggested that expression of NF-κB has an important role in H. pylori gastritis.     

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.     

Gastric mucosal proliferative and total tyrosine kinases activities increase in Helicobacter pylori-induced chronic gastritis

Background. The intestinal type of gastric cancer is thought to originate from cancer precursor lesions, progressing from H. pylori-induced chronic gastritis, atrophic gastritis, to intestinal metaplasia (IM) and dysplasia. Tyrosine kinases (tyr-k) represent the family of proteins that are widely expressed during cell metabolism and are considered as secondary markers for cellular proliferation and malignant transformation. Aim of Study. The aim of the study was to evaluate the correlation between gastric mucosal histopathologic changes, total tyrosine kinases, and proliferative activities in patients with H. pylori infection. Methods. Biopsy specimens from the gastric mucosa of 94 patients were assessed for H. pylori infection, histopathology (according to the Sydney classification), proliferative activity [Ki-67 immunohistochemistry with labeling index (LI) estimation], and total tyr-k activities (ELISA assay kit). Results. Total tyr-k activities and Ki-67 LI were significantly higher in H. pylori (+) than H. pylori (−) group (728.1±175.3 vs 360.1±44.4 pmol P/mg/min. p<0,01 and 20,0±5.8 vs 10.9±1.3 %, respectively). A significant correlation has been observed between the Ki-67 LI and total tyr-k activities in patients with and without H. pylori infection. In cases of gastritis accompanied with atrophic changes or intestinal metaplasia in H. pylori (+) patients, Ki-67 LI and total tyr-k activities were particularly high compared to chronic gastritis without atrophy or intestinal metaplasia. Conclusion. Those results suggest that tyrosine kinases may play an important role in the development of gastric mucosal hyperproliferation in H. pylori-induced gastritis and possibly in early phase of gastric carcinogenesis.     

Effects of pravastatin in murine collagen-induced arthritis

Here we evaluated whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have beneficial effects for collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type-II collagen and administered 100 mg/kg of pravastatin interperitoneally. We measured the effects of pravastatin for CIA including infiltration of macrophages at the synovial membrane and production of anti-type-II collagen antibodies and cytokines. Adverse reactions of pravastatin were also measured. The pravastatin-treated mice had delayed onset of CIA compared with the controls. The involvement of inflammatory cells in the synovial membrane and the expression of monocyte chemotactic protein-1 (MCP-1) mRNA in the joint were reduced. Moreover, some cytokines (TNF-α, IL-6, IFN-γ) and MCP-1 levels in the supernatants of spleen cells cultured with pravastatin decreased. Meanwhile, adverse reactions of pravastatin, such as peritonitis, were not detected. Pravastatin may have good prospects for treating some anti-inflammatory effects on human rheumatoid arthritis.     

Interleukin-10 (−819 C/T) and Tumor Necrosis Factor-α (−308 G/A) Gene Variants Influence Gastritis and Lymphoid Follicle Development

Helicobacter pylori (H. pylori) causes gastritis, development of lymphoid follicles and later monoclonal mucosa-associated lymphoid tissue (MALT) lymphoma. We evaluated the association of tumor necrosis factor (TNF)-α (−308 G/A) and IL-10 (−819 C/T) gene polymorphisms with gastritis and lymphoid follicle formation. H. pylori infection was detected using modified Giemsa staining and IgG anti-CagA enzyme-linked immunosorbent assay (ELISA). One hundred and thirty patients with non-ulcer dyspepsia (NUD) and 200 healthy age-matched controls were genotyped for TNF-α and IL-10 polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). Subjects with IL-10 −819 T allele [patients (46.5%) versus controls (35.7%), p = 0.006, OR = 1.56, 95% CI = 1.14–2.15] were at risk of gastritis. Infection with H. pylori was more often associated with lymphoid follicles formation than its absence (46% versus 22%, p = 0.009). TNF-α polymorphism did not influence gastritis but patients with TNF-α −308 A allele carriers showed >2 fold risk of lymphoid follicle formation [presence (26%) versus absence (11.25%), p = 0.029, OR = 2.8; 95% CI = 1.09–7.08]. There was a trend towards association of lymphoid follicles and TNF-α −308 A allele carriers with H. pylori infection than without (58.5% versus 22.2%; p = 0.064). IL-10 −819 T and TNF-α −308 A alleles may increase risk of gastritis and lymphoid follicle formation.     

Association Between Gastric Atrophy and Helicobacter pylori Infection in Japanese Children: A Retrospective Multicenter Study

The purpose of this study was to determine whether Helicobacter pylori infection and mucosal inflammation result in gastric atrophy in Japanese children. A total of 196 patients ages 1–16 years were retrospectively studied: 131 patients were infected with H. pylori and 65 patients were uninfected. Antral (n = 196) and corpus biopsy specimens (n = 70) were investigated based on the Updated Sydney system. In both the antrum and corpus, H. pylori-infected patients showed significantly higher degrees of inflammation and activity of gastritis, compared with noninfected patients. The prevalence of grade 2 or 3 atrophy in the antrum was 10.7% in H. pylori-infected patients and 0% in the noninfected patients (P < .01) and in corpus 4.3% and 0%, respectively (P = .20). The frequency of intestinal metaplasia in the 2 study groups was 4.6% and 4.6% in the antrum and 0% and 4.2% in the corpus, respectively. Among H. pylori-infected patients, the antrum showed significantly higher degrees of H. pylori density, inflammation and activity of gastritis, and atrophy than the corpus. In the antrum, atrophy was significantly correlated with activity, whereas in the corpus, atrophy correlated with H. pylori density, inflammation, and activity. H. pylori-induced gastric inflammation can cause atrophy in Japanese children, predominantly in the antrum. It remains to be determined whether H. pylori-infected children with gastric atrophy are at increased risk for gastric cancer.     

Cloning,polymorphism, and inhibition of β-carbonic anhydrase of <Emphasis Type="Italic">Helicobacter pylori</Emphasis>

Background  Carbonic anhydrase (CA) catalyzes the reversible hydration of CO₂ to bicarbonate and a proton, and α-class CA has been reported to facilitate the acid acclimation of Helicobacter pylori (hpαCA). The purpose of this study was to characterize the β-class CA of H. pylori (hpβCA) and elucidate the role of this enzyme as a possible drug target for eradication therapy. Methods  We isolated DNA clones of independent H. pylori strains obtained from patients with gastritis (n = 15), gastric ulcer (n = 6), or gastric cancer (n = 16), and then studied genetic polymorphisms. In addition, the susceptibility of H. pylori to sulpiride, an antiulcer drug and efficient inhibitor of both hpαCA and hpβCA, was studied with an in vitro killing assay. Results  DNA sequences of all 37 hpβCA clones encoded a 221 amino acid polypeptide with a variety of polymorphisms (57 types of amino acid substitution at 48 residue positions). There was no polymorphism functionally relevant to the gastric lesion type. One strain included unique residues that were not seen in the other 36 clones from Japanese patients but which were found in a strain obtained from the United Kingdom. Sulpiride had killing effects at concentrations greater than 200 μg/ml for H. pylori, including strains resistant to clarithromycin, metronidazole, or ampicillin. Conclusions   Helicobacter pylori might have evolved independently in the Caucasian and Japanese populations. Dual inhibition of α-and β-class CAs could be applied as alternative therapy for eradication of H. pylori.     

Transmission of Helicobacter pylori from Challenged to Nonchallenged Nude Mice Kept in a Single Cage

To determine the transmission route of Helicobacter pylori, one nude mouse was challenged by H. pylori, and then raised with nonchallenged nude mice in a single cage in a sterilized environment with and without exposure to their feces. After coraising for two and four weeks, all mice were killed to determine H. pylori in the stomach, saliva, and feces and to assess gastritis grade. Natural transmission of H. pylori occurred in 50% (2/4) and 70% (7/10) of mice after two weeks and four weeks of coraising when they were exposed to their feces. H. pylori was detected not only in the stomach but also in saliva and feces by PCR of all challenged and transmitted mice. However, no transmission occurred in mice not exposed to feces of a challenged mouse, while sharing food and water in a single cage. These findings suggest that the fecal–oral transmission route is important, at least in the animal model. Serum levels of anti-H. pylori urease IgG of the H. pylori-transmitted mice increased after coraising, and gastritis was observed in the stomach of both challenged and transmitted mice. We conclude that H. pylori bacteria are transmitted through the fecal–oral route from challenged to nonchallenged nude mice, resulting in gastritis.     

Gastric Emptying is Altered with the Presence of Gastritis

Helicobacter pylori infection and gastritis can cause symptoms suggestive of altered gastrointestinal function; however, it is unclear if H. pylori influences gastric motility. This study assessed gastric emptying rates in mouse models of gastritis. Gastritis was induced in C57BL/6 mice via ethanol treatment or via challenge with H. pylori or H. felis. Gastric emptying rates of nutrient and non-nutrient liquids were assessed with the non-invasive ¹³C-breath test, and the results were compared to healthy mice. Gastric emptying of the non-nutrient liquid was unaltered with the presence of gastritis; however, gastric emptying of the nutrient liquid was accelerated after a 4-week infection with H. pylori. H. felis infection and ethanol treatment caused a more severe gastritis and disruptions to the normal gastric emptying. Changes to gastric emptying in mouse models of gastritis are associated with the presence of nutrients. Altered gastric emptying may contribute to symptoms commonly reported in humans with gastritis.     

Gastric mucosal plasminogen activators inHelicobacter pylori infection

Long-termH. pylori associated gastritis is recognized as a pathogenic factor in gastric carcinogenesis. In gastric carcinomas the amount and activity of the tissue-type plasminogen activator (t-PA) have been reported to be decreased, whereas those of the urokinase-type plasminogen activator (u-PA) were increased, contributing to the neoplastic and invasive process. The present study was performed to determine t-PA and u-PA levels and activity in gastric mucosa from 102 patients and to investigate whether these levels are influenced byH. pylori infection. The antigen concentration and activity of t-PA and u-PA in corpus mucosa were low (P<0.001) compared with those in antral mucosa, although for the u-PA activity this did not reach statistical significance. InH. pylori-associated antral gastritis the mucosal t-PA antigen concentration and activity were found to be decreased (P<0.001) compared with normal mucosa, whereas inH. pylori-associated pangastritis the corpus t-PA levels were not affected. The antigen concentration and activity of u-PA were found to be significantly (P<0.005) increased, both inH. pylori-associated gastritis of antrum and corpus mucosa. Levels of u-PA in histologically normal corpus mucosa of patients with anH. pylori-associated antral gastritis were also found to be increased (P<0.05). In conclusion, the alterations in the plasminogen activator profile found inH. pylori-associated gastritis, ie, a decrease in t-PA and an increase in u-PA, show a similar tendency as the previously found alterations in gastric carcinomas, which provides additional support for the possible involvement ofH. pylori-associated gastritis in the pathogenesis of gastric carcinoma.     

Stem Cell Factor Expressed in Human Gastric Mucosa in Relation to Mast Cell Increase in Helicobacter pylori-Infected Gastritis

We previously reported mast cell increases in H. pylori gastritis. To determine the mechanism, we investigated the kinetics of mast cells and mast cell growth factor (stem cell factor, SCF) in H. pylori-positive and -negative gastric mucosa. Biopsy specimens from 12 H. pylori-negative and 28 positive subjects were examined. Sections were stained for mast cells, proliferating cell nuclear antigen (PCNA), and SCF. Densities of mast cells, PCNA-positive mast cells, and SCF-positive cells were significantly greater in H. pylori-positive than -negative subjects. SCF was expressed in mast cells and fibroblasts. The density of SCF-positive fibroblasts increased in H. pylori-positive gastritis and decreased after cure of infection. SCF mRNA was detected in H. pylori-positive gastric mucosa. Fibroblasts isolated from the normal gastric mucosa expressed SCF mRNA after incubation with H. pylori water extract. SCF may be one of the factors for mast cell increase. Fibroblasts may participate in mast cell increase and inflammation in H. pylori infection.     

Atrophic Corpus Gastritis and Helicobacter pylori Infection in Primary Biliary Cirrhosis

Chronic atrophic corpus gastritis, termed as autoimmune corpus gastritis or type A gastritis, and primary biliary cirrhosis (PBC) are characterized by a common immunological process against the exocrine glandular structures of both the stomach and bile duct. However, there has been controversy over whether atrophic corpus gastritis is associated with PBC. Recently, it has been suggested that Helicobacter pylori plays an important role in the early stage of atrophic corpus gastritis due to the induction of autoantibodies that are reactive with a protein in the gastric parietal cells. One hypothesis is that molecular mimicry, possibly resulting from H. pylori infection, might be responsible for initiating an autoimmune response in a predisposed host due to cross-reactivity among gastric mucosal, bile ductular, and bacterial antigens. The aim of this study is to assess whether atrophic changes of the gastric corpus could affect patients with PBC, and to determine the correlation with H. pylori infection. Sixteen patients with PBC were enrolled in this study. All patients were examined by serological studies of anti-pyruvate dehydrogenase (PDH) antibody, anti-H. pylori antibody, gastrin and vitamin B₁₂. Gastroscopy was performed on all patients in order to verify the histological findings and to microscopically identify H. pylori. Atrophic corpus gastritis was found in 2 of 16 patients with PBC (12.5%), one of whom was confirmed to have pernicious anemia, a developed stage of atrophic corpus gastritis. H. pylori infection in the gastric corpus and the anti-H. pylori antibody were found in 7 (43.8%) and 11 (68.8%) of 16 patients, respectively. Anti-H. pylori antibody was confirmed to be positive in both of the patients with atrophic corpus gastritis, although H. pylori was absent in the gastric biopsy specimen. There was a positive correlation between anti-PDH antibodies and anti-H. pylori antibodies in sera from patients with PBC. Atrophic corpus gastritis is not frequently involved in PBC. However, H. pylori is a possible pathogenic factor in atrophic corpus gastritis in PBC patients because of the presence of anti-H. pylori antibody. A positive correlation between the titer of anti-PDH antibodies and the titer of anti-H. pylori antibodies was confirmed. Consequently, H. pylori infection could induce autoimmune responses in the development of both PBC and atrophic corpus gastritis. H. pylori infection associated with PBC requires further study.     

Serum and Tissue Beta-2 Microglobulin Levels in Patients with Helicobacter pylori Infection

Background and aim Beta-2 microglobulin (β₂-m) is a minor plasma protein, secreted from the plasma membranes as a result of the continuous regeneration of membrane proteins in the cell surface of all nucleated cells. The relationship between Helicobacter pylori and β₂-m has not been adequately established in studies. In this study, we aimed to compare the levels of serum and tissue β₂-m in patients with and without H. pylori infection, and to examine the relationship between levels of serum and tissue β₂-m. Material and methods About 30 patients with H. pylori gastritis and 22 healthy persons were enrolled in this study. Gastric biopsies were histologically analyzed and compared according to tissue and serum β₂-m levels. Results Serum β₂-m levels were comparable in H. pylori and control groups. There was no significant link between tissue H. pylori grade and serum β₂-m levels. Subendothelial β₂-m was detected in 19 (63.3%) cases with H. pylori and none of the control group with immunohistochemical staining (P < 0.001). There was no correlation between serum and tissue levels of β₂-m. Conclusion β₂-m accumulates in the majority of gastric tissues of patients with active chronic gastritis who were H. pylori (+), whereas no accumulation was found in H. pylori (−) control subjects.     

Helicobacter pylori and gut hormones

Helicobacter pylori infection has been found to decrease the expression of antral somatostatin and to increase the release of the acid-stimulating hormone gastrin. The reversal of these changes in gut hormones by the eradication of H. pylori, and in-vivo and in-vitro studies in animals either infected with H. pylori or exposed to H. pylori-related materials may support the somatostatin-gastrin link theory in the pathophysiology of H. pylori infection. The following mechanisms have been proposed to explain the H. pylori infection-associated changes in gut hormones; (1) ammonia produced by H. pylori and monochloramine, (2) effect on somatostatin receptor subtype-2, (3) action of lipopolysaccharide from H. pylori on somatostatin receptor, (4) inflammatory cells and mediators, and (5) bacterial strain diversity. H. pylori infection can alter gastric acid secretion in both directions. The elevated acid secretion in patients with duodenal ulcer is decreased by H. pylori eradication, and is accompanied by the normalization of gut hormones in patients whose H. pylori-induced gastritis is limited to the antrum with hyperacidity. Corpus gastritis and the subsequent development of mucosal atrophy induced by H. pylori result in decreased acid secretion, although the mechanism underlying H. pylori-induced atrophy in some subjects remains unclear. Hypoacidity enhances corpus atrophy and increases gastrin secretion, mediated via a physiological suppression of somatostatin release, features that are also observed in H. pylori infection. Therefore, the capacity of acid secretion and distribution of gastritis or atrophy should be taken into consideration when we discuss the affect of H. pylori on gut hormones. Received: October 1, 2001 / Accepted: November 30, 2001     

Helicobacter pylori cagA Status and Peptic Ulcer Disease in Iran

Helicobacter pylori contributes to the development of peptic ulcers and atrophic gastritis. Furthermore, H. pylori strains carrying the cagA gene are more virulent than cagA -negative strains and are associated with the development of gastric adenocarcinoma. The cagA gene is a putative H. pylori virulence factor of unknown function. The aim of this study was to determine the prevalence of the cagA gene among H. pylori isolates and its relationship with peptic ulcer disease in 128 Iranian patients. A total of 107 (83.6%) samples were positive, including 40 (95%) of the 42 patients with duodenal ulcer, 43 (86%) of the 50 patients with gastric ulcer, and 24 (66.6%) of the 36 patients with gastritis. cagA was present in 32 (80%) of 40 strains from duodenal ulcer patients, 33 (77%) of 43 strains from gastric ulcer patients, and 11 (46%) of 24 from gastritis patients. We also attempted to investigate the subtypes of 3′ region of cagA gene in H. pylori strains isolated from Iranian patients and their relation to H. pylori-associated gastroduodenal diseases. The PCR product of cagA positive strains obtained with primer set CAG1/CAG2 differed in size, varying from 642 to 651 bp (subtype A) in 33 isolates to 756 bp (subtype B/D) in 13 isolates. This does not support the view that subtypes of the 3′ region of cagA gene in H. pylori isolated from Iran correlate with the clinical outcomes of H. pylori, but colonization with cagA positive strains was significantly higher among duodenal ulcer than gastritis patients in Iran.     

Helicobacter pylori prevents proliferative stage of angiogenesis in vitro: role of cytokines

Inhibition of angiogenesis may explain the delayed ulcer healing following Helicobacter pylori infection. We have previosuly demonstrated that H. pylori can inhibit endothelial cell proliferation. Some cytokines possess antiangiogenic properties. This study assessed a role for IL-6, IL-8, and TNF- in H. pylori-induced endothelial cytostasis. First, 30 l of H. pylori was coincubated with microvascular endothelial cells in the presence or absence of monoclonal antibodies to IL-6, IL-8, and TNF- for 24, 48, 72, or 96 hr. Dual labeling with propidium iodide and Hoescht 33342 distinguished between necrosis, and apoptosis and allowed viable cell numbers to be determined. H. pylori decreased cell viability after 72 and 96 hr (P < 0.02). Neither necrosis nor apoptosis was observed. Monoclonal antibodies to IL-6 and IL-8 did not reverse cytostasis. However, significant MVEC proliferation was observed in the presence of the TNF- monoclonal antibody. In conclusion, H. pylori induces cytokine up-regulation as part of its pathophysiological mechanism, which could prove detrimental to ulcer healing through an inhibitory effect on angiogenesis.     

Suppressive effect of rice extract on Helicobacter pylori infection in a Mongolian gerbil model

Background Rice extract has been shown to protect gastric mucosa from stress-induced damage. In this study, the antibiotic effect and the anti-inflammatory effect of orally administered aqueous rice extract on Helicobacter pylori infection and H. pylori-induced gastritis, respectively, in Mongolian gerbils were investigated.Methods Fifty specific-pathogen-free male Mongolian gerbils, seven weeks old, were divided into four groups: uninfected, untreated animals (group A); uninfected, rice extract-treated animals (group B); H. pylori-infected, untreated animals (group C); and H. pylori-infected, rice extract-treated animals (group D). Group C and D animals were killed 12 weeks after H. pylori infection (i.e., at 19 weeks of age) and group A and B animals were also killed at age 19 weeks. The stomachs were removed for histopathological examination with hematoxylin-and-eosin staining and anti-5-bromo-2-deoxyuridine (BrdU) immunostaining, and to determine the bacterial burden. Serum anti-H. pylori antibody titers were also tested.Results In groups A and B, the gastric mucosa showed no inflammatory cell infiltration and a few BrdU-reactive cells. Group C animals developed marked chronic active gastritis in the gastric mucosa, and BrdU-labeled cells in the gastric mucosa markedly increased in number. In group D animals, a significant reduction occurred in the degree of neutrophilic polymorphonuclear cell infiltration into the gastric mucosa, in the BrdU-labeling indices of gastric epithelial cells, and in anti-H. pylori antibody titers in the serum (P < 0.01), compared with although H. pylori was not completely eradicated.Conclusions The rice extract was effective in suppressing inflammation and epithelial cell proliferation in the gastric mucosa in H. pylori-infected Mongolian gerbils. The rice extract has potential to exhibit a protective effect on H. pylori-related gastric mucosal diseases.