Tadashi Kodama

Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains

Background —Helicobacter pyloristrains possessing the cagA gene are thought to induce interleukin 8 (IL-8) in gastric mucosa. However, it is still unclear whether a relation exists between the cagA gene and the expression patterns of cytokines other than IL-8. Aims —To investigate the relation between the cagA gene and the production of various cytokine proteins using an enzyme linked immunosorbent assay (ELISA). Patients and methods —In 184 patients, the cagA gene was detected by polymerase chain reaction (PCR), and levels of production of IL-1β, IL-6, IL-7, IL-8, IL-10, and tumour necrosis factor α (TNF-α) in antral biopsy specimens were measured by ELISA. Results—Mucosal levels of IL-1β, IL-6, IL-8, and TNF-α were significantly higher in H pyloripositive than in H pylori negative patients. Furthermore, the mucosal levels of IL-1β and IL-8 were significantly higher in specimens infected with cagApositive strains than in those infected with cagAnegative strains. In H pylori positive patients, the mucosal level of IL-8 was closely correlated with that of IL-1β (p<0.0001), and the mucosal level of IL-6 was closely correlated with that of TNF-α (p<0.0001). Conclusion—These findings suggest that the ability to induce cytokines differs among the strains;cagA + strains induce various kinds of cytokines and may cause severe inflammation, whereascagA − strains induce IL-8 and IL-1β only weakly and may cause only mild inflammation. However, as most patients infected with the cagA + strains have gastritis, these strains may not be equivalent to ulcerogenic strains.

Chemokines in the gastric mucosa in Helicobacter pylori infection

Background—Although chemokines have been suggested to play an important role in Helicobacter pyloriassociated gastritis, few studies have investigated the role of chemokines other than interleukin 8 (IL-8) in gastric mucosa. Aims—To investigate the expression and production patterns of various chemokines using gastric biopsy specimens. Methods—In 192 patients, expression patterns of C-X-C chemokines (IL-8 and growth regulated α (GROα)) and C-C chemokines (regulated on activation, normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein 1α (MIP-1α), and MIP-1β) were examined using reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA).cagA gene was identified using PCR. Results—H pylori infection was associated with increased rates of expression of mRNA for IL-8, GROα, RANTES, and MIP-1α and with increased levels of mucosal IL-8 and GROα. IL-8 and GROα levels correlated with the density of H pylori in both the antrum and corpus. The levels of these chemokines correlated with cellular infiltration in the antrum but not the corpus. cagA gene positive H pyloriinfection was associated with increased rates of expression of mRNA for IL-8 and GROα and with increased levels of these chemokines. Conclusion—H pylori infection is associated with increased expression rates and production of C-X-C chemokines (IL-8 and GROα), but not with increased production of C-C chemokines. Although H pylori infection is associated with increased C-X-C chemokines in the antrum and corpus, there is a difference in the inflammatory response between these two areas of the stomach.

Helicobacter pylori in North and South America before Columbus

We present a molecular epidemiologic study, based on an analysis of vacA, cagA and cag right end junction genotypes from 1042 Helicobacter pylori isolates, suggesting that H. pylori was present in the New World before Columbus. Eight Native Colombian and Alaskan strains possessed novel vacA and/or cagA gene structures and were more closely related to East Asian than to non‐Asian H. pylori. Some Native Alaskan strains appear to have originated in Central Asia and to have arrived after strains found in South America suggesting that H. pylori crossed the Bering Strait from Asia to the New World at different times.

Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome.

Mosaicism in vacA alleles with three distinct families of vacA signal sequences (s1a, s1b and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. It was suggested that the vacA s1a genotype was closely associated with duodenal ulcer disease and with high cytotoxin production. The aim of this study was to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, cytotoxin activity, and clinical presentation.

Antimicrobial Activity of Essential Oils against Helicobacter pylori

Background. Helicobacter pylori is an important pathogen responsible for gastroduodenal diseases in humans. Although the eradication of H. pylori using antibiotics often improves gastroduodenal diseases, resistance to the antibiotics is emerging.

Relation between clinical presentation, Helicobacter pylori density, interleukin 1β and 8 production, and cagA status

BACKGROUND It is not known whethercagA+ Helicobacter pylori in duodenal ulcer (DU) have enhanced virulence compared with non-DU cagA+ H pylori. AIMS To investigate the relation between presentation, H pylori density, interleukin 1β (IL-1β) and IL-8 production, andcagA status. METHODS Fifty DU and 50 gastritis patients with cagA+ H pylori and 11 with cagA− infections were studied. Bacterial density and cytokine production were assessed using the same biopsies. Cytokine production was also measured from supernatants of medium following coculture of H pylori with MKN-45 cells. RESULTS There was no relation between H pylori density andcagA status. There was a dose dependent relation between mucosal cytokine levels and density ofcagA+ H pylori. H pylori density increased to a threshold, followed by a rapid increase in cytokines and then a plateau. IL-1β and IL-8 levels in the antrum were greater in DU than in gastritis; in the corpus the cytokine level/H pylori differed irrespective of similar H pylori densities. However, cytokine production was similar in vitro, independent of presentation or biopsy site, suggesting that host factors are critical determinants of the inflammatory response. Mucosal IL-8 and IL-1β levels were low withcagA− andcagA+, cagE− H pylori infections. CONCLUSIONS The increase in antral IL-1β and IL-8 production and inflammation in DU is related to increased numbers of bacteria and not to an increase in cytokine production per cagA+ isolate. There was no evidence of enhanced virulence of H pylorifrom DU compared with cagA+ non-DUH pylori.

Endoscopic papillary balloon dilatation may preserve sphincter of Oddi function after common bile duct stone management: evaluation from the viewpoint of endoscopic manometry

Background—Endoscopic papillary balloon dilatation (EPBD) has been reported as a safe and effective alternative to endoscopic sphincterotomy in the management of common bile duct (CBD) stones; its effect on papillary function has yet to be elucidated. Aim—To investigate sphincter of Oddi (SO) motility before and after EPBD to determine its effect on SO function. Patients and methods—The papillary function of 10 patients with CBD stones was studied using endoscopic manometry before and one week after EPBD. The manometric studies were repeated one month after EPBD in seven patients. Results—One week after EPBD, CBD pressure, SO peak pressure, SO basal pressure, and SO frequency decreased significantly. One month after EPBD, however, all parameters increased although the increases in SO basal pressure and CBD pressure were not significant. There was no significant difference in values of any parameter before and one month after EPBD. No serious complications occurred. Conclusion—These data suggest at least partial recovery of papillary function one month after the procedure. EPBD seems to preserve papillary function in treatment of CBD stones; a longer term follow up study with SO manometry should be performed to clarify the effect of EPBD on SO function.

Discrimination between Cases of Duodenal Ulcer and Gastritis on the Basis of Putative Virulence Factors of Helicobacter pylori

ABSTRACT The BabA, cagA, and vacA statuses of 827 Helicobacter pylori isolates were used in logistic regression models to discriminate duodenal ulcer from gastritis. Only BabA was a candidate for a universal virulence factor, but the low c statistic value (0.581) indicates that none of these factors were helpful in predicting the clinical presentation.

Relation between Cytokines and Helicobacter pylori in Gastric Cancer

Helicobacter pylori is etiologically involved in the development of gastric cancer and infected gastric mucosa has been shown to possess elevated levels of cytokines [for example interleukin (IL)‐1β, IL‐6 and IL‐8]. Because specific cytokines have also been shown to enhance the development of certain cancers, we examined the relationship between the levels of cytokines, the type and stage of gastric cancers, and the H. pylori infection.

Cytokine Expression and Production by Purified Helicobacter pylori Urease in Human Gastric Epithelial Cells

ABSTRACT Cytokines have been proposed to play an important role inHelicobacter pylori-associated gastroduodenal diseases, but the exact mechanism of the cytokine induction remains unclear. H. pylori urease, a major component of the soluble proteins extracted from bacterial cells, is considered to be one of the virulence factors for the inflammation in the gastric mucosa that is produced in H. pylori infection. However, the response of human gastric epithelial cells to the stimulation of urease has not been investigated. In the present study, we used human gastric epithelial cells in a primary culture system and examined whetherH. pylori urease stimulates the gastric epithelial cells to induce proinflammatory cytokines by reverse transcription-PCR and enzyme-linked immunosorbent assay. First, by using peripheral blood mononuclear cells (PBMC) and a gastric cancer cell line (MKN-45 cells), we confirmed the ability of purified H. pylori urease to induce the production of proinflammatory cytokines. Furthermore, we demonstrated that the human gastric epithelial cells produced interleukin-6 (IL-6) and tumor necrosis factor alpha, but not IL-8, following stimulation with purified urease. The patterns of cytokine induction differed among human PBMC, MKN-45 cells, and human gastric epithelial cells. These results suggest that the human gastric epithelial cells contribute to the induction of proinflammatory cytokines by the stimulation of H. pylori urease, indicating that the epithelial cells were involved in the mucosal inflammation that accompanied H. pylori infection.