Mucosal interleukin-21 mRNA expression level is high in patients with Helicobacter pylori and is associated with the severity of gastritis.

Helicobacter pylori (H. pylori) infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells. Different clinical forms of the infection may reflect distinctive patterns of cytokine expression. Interleukin (IL)-17, IL-21, IL-22, and IL-23 have been reported to be involved in H. pylori-induced gastric mucosal inflammation, but the details and relationship to different patterns of inflammation and virulence factors remain unclear. The present study was launched to analyse IL-6 expression in H. pylori-infected and uninfected gastric patients and to investigate its correlation with chronic gastritis among H. pylori-infected patients. Total RNA was extracted from the gastric antrum biopsies of 48 H. pylori-infected patients and 38 H. pylori uninfected patients. Mucosal IL-21 mRNA expression level in H. pylori-infected and uninfected gastric biopsy was determined by real-time PCR. The presence of vacA (vacuolating cytotoxin A) and cagA (cytotoxin associated gene A) virulence factors were evaluated using PCR. Interleukin-21 mRNA expression was significantly high in biopsies of H. pylori-infected patients compared to H. pylori uninfected patients, and the mucosal IL-21 mRNA level was positively correlated with the grade of chronic inflammation. There was no association between virulence factors and IL-21 mRNA expression. We believe that IL-21 might be involved in the pathogenesis of H. pylori and might be an index of the severity of chronic gastritis.

Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-ß1 mRNA expression in gastritis patients.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-ß1 was shown to be secreted in a subset of Treg cells known as 'Th3 cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-ß1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors. PATIENTS AND METHODS: Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-ß1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR. RESULTS: TGF-ß1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-ß1 mRNA expression. TGF-ß1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1. CONCLUSIONS: TGF-ß1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-ß1 mRNA.

Association between virulence factors of helicobacter pylori and gastric mucosal interleukin-18 mRNA expression in dyspeptic patients.

BACKGROUND: Helicobacter pylori (Hp) infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells that contribute to sustain and expand the local inflammation. Different clinical expressions of the infection may reflect distinctive patterns of cytokine expression. IL-1ß, TNF-α, IL-17 and IL-23 have been reported to be involved in Hp-induced gastric mucosal inflammation, but the details and association to different patterns of inflammation and virulence factors remain unclear. METHODS: Total RNA was extracted from gastric biopsies of 51 Hp-infected patients and 44 Hp-negative patients. Mucosal IL-18 mRNA expression in gastric biopsies was determined by Real-Time PCR. Presence of virulence factors was evaluated using PCR. RESULTS: IL-18 mRNA expression was significantly increased in biopsies of Hp-infected patients compared to Hp-uninfected individuals. There was no association between virulence factors and IL-18 mRNA expression. Also severity of mononuclear infiltration was significantly higher in gastritis patients with vacA (m1)-positive compare patients with vacA (m2)-positive. CONCLUSIONS: IL-18 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the stomach. This may ultimately influence the outcome of Hp-associated diseases that arise within the context of gastritis.

Associations of a TLR4 single-nucleotide polymorphism with H. pylori associated gastric diseases in Iranian patients.

OBJECTIVE: Helicobacter pylori (H. pylori) is associated with gastric ulcer and gastric adenocarcinoma. Polymorphisms in the host genes coding for toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. But the details and association to different polymorphisms and different clinical expressions in patients infected with H. pylori (different clinical expression of H. pylori infection) remain unclear. METHODS: A case-control study consisting of 195 patients with H. pylori infection and 241 H. pylori uninfection was conducted. Genomic DNA was extracted and genotypes of TLR4Asp299Gly polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Presence of cagA was evaluated using PCR. RESULTS: TLR4 (Asp299Gly) G and DG alleles frequency in H. pylori infected population was significantly higher in the chronic gastritis group than in the chronic active gastritis group (P=0.021; OR, 2.409; 95% CI, 1.124-5.162). Grade mononuclear (MN) infiltration in H. pylori infected patients with DG genotype of TLR-4 Asp299Gly increased significantly. CagA positivity was more frequently associated with chronic active gastritis (P=0.017, OR=2.26, 95% CI=1.144-4.462) and grade polymorphonucler (PMN) infiltration. CONCLUSION: TLR-4 Asp299Gly G allele substitution may be modified pattern of immune response in the gastric mucosa of H. pylori infected patients and may be H. pylori infected patients with gastritis have increased risk for the development of chronic gastritis. CagA positivity may be a risk factor for development of gastritis.

Association of the virulence factors of Helicobacter pylori and gastric mucosal interleukin-17/23 mRNA expression in dyspeptic patients.

The molecular pathways that control Helicobacter pylori (Hp)-associated inflammatory reaction are complex, but locally induced cytokines and virulence factors seem to have a major role in maintaining the ongoing inflammation. Therefore this study was aimed to evaluate the association of the virulence factors of Hp and gastric mucosal interleukin-17/23 mRNA expression in dyspeptic patients. Mucosal IL-17 and IL-23 mRNA expression in H. pylori infected and non-infected gastric biopsies were determined by real-time RT-PCR. Virulence factors, vac-A and cag-A were evaluated using PCR. There was no significant difference in mucosal IL-17 and IL-23 mRNA expression between H. pylori infected and non-infected patients. Their expression in mucosa did not correlate with chronic gastritis and chronic active gastritis. IL-17 and IL-23 mRNA expression in mucosa of patients with vacA m1 were significantly higher than those observed in patients with vacA m2. The severity of polymorphonuclear infiltration and chronic active gastritis was higher in cag-A positive than cag-A negative patients. H. pylori infections carrying the vacA m1 allele have higher IL-17 and IL-23 mRNA and the current study suggests that the virulence factor vacA allele's m1 are important for the severe gastric inflammation.