Nader Bagheri

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

BACKGROUNDnHelicobacter 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-1β, 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.nnnMETHODSnTotal 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.nnnRESULTSnIL-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.nnnCONCLUSIONSnIL-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.

Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients

OBJECTIVEnHelicobacter 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-β1 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.xa0pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-β1 in the context of H.xa0pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors.nnnPATIENTS AND METHODSnTotal RNA was extracted from gastric biopsies of 48 H.xa0pylori-infected patients and 38 H.xa0pylori-negative patients with gastritis. Mucosal TGF-β1 mRNA expression in H.xa0pylori-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.nnnRESULTSnTGF-β1 mRNA expression was significantly increased in biopsies of H.xa0pylori-infected patients compared to H.xa0pylori-uninfected patients. There was association between virulence factors and TGF-β1 mRNA expression. TGF-β1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1.nnnCONCLUSIONSnTGF-β1 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.xa0pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-β1 mRNA.

The biological functions of IL-17 in different clinical expressions of Helicobacter pylori-infection.

Helicobacter pylori (H.xa0pylori) infection is regarded as the major cause of various gastric diseases (gastritis, peptic ulcers and gastric cancer) and induces the production of several cytokines. Interleukin-17 (IL-17) is recently recognized as an important player in the pathophysiology of infectious and immune-mediated gastrointestinal diseases. H.xa0pylori infection increases IL-17 in the gastric mucosa of humans. IL-17 usually causes secretion of IL-8 through activation of ERK 1/2 MAP kinase pathway. The released IL-8 attracts neutrophils promoting inflammation. T regulatory cells (Tregs) suppress the inflammatory reaction driven by IL-17, there by favoring bacterial persistence in H.xa0pylori-infection. The pathogenesis of H.xa0pylori-induced inflammation is not well understood. Inflammation is promoted by both host factors and H.xa0pylori factors, such as the proteins cytotoxin associated gene A (cagA) and vacuolating cytotoxin A (vacA). IL-1β, IL-6, tumor necrosis factor (TNF)-α, TGF-β1, IL-17, IL-18, IL-21 and IL-22 have been reported to be involved in H.xa0pylori-induced gastric mucosal inflammation, but the details and relation to different patterns of inflammation remain unclear. Numerous studies have demonstrated important functions of IL-17 in acute and chronic inflammatory processes. This paper reviews the role of IL-17 in gastritis, peptic ulcers and gastric cancer related to H.xa0pylori.

FREQUENCY OF VIRULENCE FACTORS IN HELICOBACTER PYLORI-INFECTED PATIENTS WITH GASTRITIS

UNLABELLEDnThe outcome of Helicobacter pylori infection has been related to specific virulence-associated bacterial genotypes. The vacuolating cytotoxin (vacA), cagA gene, oipA and babA2 gene are important virulence factor involving gastric diseases. The objective of this study was to assess the relationship between virulence factors of H. pylori and histopathological findings.nnnMATERIAL AND METHODSnGastroduodenoscopy was performed in 436 dyspeptic patients. Antrum biopsy was obtained for detection of H. pylori, virulence factors and for histopathological assessment. The polymerase chain reaction was used to detect virulence factors of H. pylori using specific primers.nnnRESULTSnvacA genotypes in patients infected with H. pylori were associated with cagA, iceA1 and iceA2. In the patients with H. pylori infection there was a significant relationship between cagA positivity and neutrophil activity (P = 0.004) and chronic inflammation (P = 0.013) and with H. pylori density (P = 0.034). Neutrophil infiltration was found to be more severe in the s1 group than in the s2 group (P = 0.042). Also was a significant relationship between oipA positivity and neutrophil activity (P = 0.004) and with H. pylori density (P = 0.018). No significant relationships were observed between other vacA genotypes and histopathological parameters.nnnCONCLUSIONnH. pylori strains showing cagA, vacA s1 and oipA positivity are associated with more severe gastritis in some histological features but virulence factors of H. pylori do not appear to determine the overall pattern of gastritis.

Comparative Immune Response in Children and Adults with H. pylori Infection

Helicobacter pylori (H. pylori) infection is generally acquired during early childhood; therefore, the immune response which usually takes place at this age may influence or even determine susceptibility to the infection contributing to the clinical outcomes in adulthood. Several cytokines including IL-6, IL-10, and TGF-β1 as well as Foxp3+ cell numbers have been shown to be higher; however, some other cytokines consisting of IL-1β, IL-17A, and IL-23 are lower in infected children than in infected adults. Immune response to H. pylori infection in children is predominant Treg instead of Th17 cell response. These results indicate that immune system responses probably play a role in persistent H. pylori infection. Childhood H. pylori infection is also associated with significantly lower levels of inflammation and ulceration compared with adults. This review, therefore, aimed to provide critical findings of the available literature about comparative immune system in children and adults with H. pylori infection.

ASSOCIATIONS OF A TLR4 SINGLE-NUCLEOTIDE POLYMORPHISM WITH H. PYLORI ASSOCIATED GASTRIC DISEASES IN IRANIAN PATIENTS

OBJECTIVEnHelicobacter pylori (H.xa0pylori) 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.xa0pylori or the disease outcomes. But the details and association to different polymorphisms and different clinical expressions in patients infected with H.xa0pylori (different clinical expression of H.xa0pylori infection) remain unclear.nnnMETHODSnA case-control study consisting of 195 patients with H.xa0pylori infection and 241 H.xa0pylori 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.nnnRESULTSnTLR4 (Asp299Gly) G and DG alleles frequency in H.xa0pylori 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.xa0pylori 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.nnnCONCLUSIONnTLR-4 Asp299Gly G allele substitution may be modified pattern of immune response in the gastric mucosa of H.xa0pylori infected patients and may be H.xa0pylori infected patients with gastritis have increased risk for the development of chronic gastritis. CagA positivity may be a risk factor for development of gastritis.

Altered Th17 Cytokine Expression in Helicobacter pylori Patients with TLR4 (D299G) Polymorphism

ABSTRACT 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. However, the details and association with different polymorphism and clinical expression of infection remain unclear. A case-control study consisting of 58 patients with H. pylori infection and 44 H. pylori uninfection was conducted. Genomic DNA was extracted and genotypes of TLR4 Asp299Gly polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mucosal cytokines expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. The expression of IL-6, IL-17, IL-21, IL-23 and TGF-β1 was significantly higher in patients with D299G polymorphism in TLR4. But the expression of IL-18 between patients with single-nucleotide polymorphisms (SNPs) in TLR4 and patients with the wild-type allele was not significant. In H. pylori-infected patients with gastritis, SNPs in TLR4 may alter cytokine expression toward Th17 immune response in the gastric mucosa and may have increased risk for the development of peptic ulcer.

The role of Th1 and Th17 cells in glomerulonephritis

Context: T helper (Th) cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Evidence Acquisitions: Directory of open access journals (DOAJ), Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Results: Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Conclusions: Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis.

Correlation Between Mucosal IL-6 mRNA Expression Level and Virulence Factors of Helicobacter pylori in Iranian Adult Patients With Chronic Gastritis

Background: Helicobacter pylori infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells that contribute to sustained local inflammation. In this study, we sought to examine IL-6 expression in H. pylori-infected and uninfected gastric mucosa and elucidate the implication in the pathogenesis of H. pylori-associated gastritis in human. Objectives: The current study aimed to determine mucosal IL-6 mRNA expression level and their correlation with virulence factors and the grade of chronic gastritis among H. pylori infected patients with chronic gastritis from Shahrekord, Iran. Patients and Methods: Mucosal IL-6 mRNA levels was measured by real-time PCR using endoscopic biopsies taken from the gastric antrum of 58 subjects infected with H. pylori and 44 uninfected subjects. Presence of vacA and cagA virulence factors was evaluated using PCR. Results: The IL-6 mRNA expression levels were significantly more elevated in H. pylori-positive patients than uninfected individuals and expression of this cytokine was independent from the virulence factors. There was a correlation between IL-6 expression level and the grade of chronic gastritis. Conclusions: Enhanced induction of IL-6 may be involved in the pathogenesis of H. pylori-associated gastritis.

Study of VSX1 Mutations in Patients with Keratoconus in Southwest Iran Using PCR-Single-Strand Conformation Polymorphism/Heteroduplex Analysis and Sequencing Method

Objective: Keratoconus (KC) is an eye disorder in which the cornea is swollen, thinned and deformed. Despite extensive studies, the pathophysiological processes and genetic etiology of KC are unknown. The disease incidence is approximately 1 in 2,000, and it is the most common cause of corneal transplantation in the USA. Many genes are involved in the disease, but evidence suggests a major role for VSX1 in the etiology of KC. This study aimed to determine the frequency of mutations in exons 2, 3 and 4 of the VSX1 gene in Chaharmahal va Bakhtiari province in the southwest of Iran. Study Design: In this experimental study, mutations in 3 exons, namely exons 2, 3 and 4, of VSX1 were investigated in 50 patients with KC and 50 healthy control subjects. DNA was extracted using a standard phenol-chloroform method. PCR-single-strand conformational polymorphism/heteroduplex analysis was performed, followed by DNA sequencing to confirm the identified motility shifts. Results: H244R mutations were found in 1 patient and also in 1 healthy control subject. Furthermore, 12 polymorphisms were identified in patients with KC and 7 in healthy control subjects [rs6138482 and c.546A>G (rs12480307)]. Conclusion: Our investigation showed that KC-related VSX1 mutations were found in a very small proportion of the studied patients from Iran. Further investigations on other genes are needed to clarify their roles in KC pathogenesis.