Inflammatory Process In Gastric Mucosa Research Articles

Role of genetic structure of Helicobacter Pylori in formation of chronic inflammatory process in gastric mucosa

The literature review highlights the questions of the interaction of Helicobacter pylori and the human body. Modern data on the structure of the pathogenicity island in the Helicobacter pylori genome are presented. There is given a detailed description of both well-known virulence and pathogenicity factors of the infection (genes encoding the formation of urease subunits, in particular urel, cytotoxin associated gene A, vacuolating cytotoxin gen A, blood group associated binding adhesion, induced by contact with epithelium) and less studied ones (sialic acid-binding adhesion, adhesion-associated lipoprotein A and B, adhesin gene of Helicobacter pylori, Hp outer membrane protein). The significance of individual genes and proteins encoded by them in the development of chronic inflammatory process in diseases of the upper digestive tract, as well as in ulcer and carcinogenesis is analyzed. Mechanisms of interaction of bacteria with epithelial cells of the gastric mucosa, adhesive and cytotoxic effects of Helicobacter pylori, factors of biofilm formation are described. The influence of the genetic structure of Infect on cytological composition of the gastric glands in the form of reduction of specialized glandular cells chief and parietal cells of pyloric glands and the increase of endocrine cells in the pool is assessed. It is shown that colonization of the gastric mucosa by highly pathogenic strains of Helicobacter pylori contributes to the development of widespread pronounced and active inflammation in it, the appearance of morphological signs of atrophy. The role of the genetic characteristics of the infection in the failure of anti-helicobacter therapy is emphasized. Separately, the question of the effect of combined infection of the gastric mucosa with highly pathogenic strains of Helicobacter pylori and Epstein-Barr virus is highlighted.

NKX6.3 protects against gastric mucosal atrophy by downregulating β-amyloid production.

BACKGROUNDAtrophic gastritis is characterized by loss of appropriate glands and reduction in gastric secretory function due to chronic inflammatory processes in gastric mucosa. Moreover, atrophic gastritis is considered as a precancerous condition of gastric cancer. However, little is known about the molecular mechanism underlying gastric mucosal atrophy and its contribution to gastric carcinogenesis. Thus, we hypothesized that transcription factor NKX6.3 might be involved in maintaining gastric epithelial homeostasis by regulating amyloid β (Aβ) production.AIMTo determine whether NKX6.3 might protect against gastric mucosal atrophy by regulating Aβ production.METHODSWe identified NKX6.3 depletion induced cell death by cell count and Western blot assay. Production and mechanism of Aβ oligomer were analyzed by enzyme-linked immunosorbent assay, Western blot, immunoprecipitation, real-time quantitative polymerase chain reaction and immunofluorescence analysis. We further validated the correlation between expression of NKX6.3, Helicobacter pylori CagA, Aβ oligomer, apolipoprotein E (ApoE), and β-secretase 1 (Bace1) in 55 gastric mucosae.RESULTSNKX6.3 depletion increased both adherent and floating cell populations in HFE-145 cells. Expression levels of cleaved caspase-3, -9, and poly ADP ribose polymerase were elevated in floating HFE-145shNKX6.3 cells. NKX6.3 depletion produced Aβ peptide oligomers, and increased expression of ApoE, amyloid precursor protein, Aβ, Bace1, low-density lipoprotein receptor, nicastrin, high mobility group box1, and receptor for advanced glycosylation end product proteins. In immunoprecipitation assay, γ-secretase complex was stably formed only in HFE-145shNKX6.3 cells. In gastric mucosae with atrophy, expression of Aβ peptide oligomer, ApoE, and Bace1 was detected and inversely correlated with NKX6.3 expression. Treatment with recombinant Aβ 1-42 produced Aβ oligomeric forms and decreased cell viability in HFE-145shNKX6.3 cells. Additionally, NKX6.3 depletion increased expression of inflammatory cytokines and cyclooxygenase-2.CONCLUSIONNKX6.3 inhibits gastric mucosal atrophy by regulating Aβ accumulation and inflammatory reaction in gastric epithelial cells.

Peculiar features of inflammatory process in gastric mucosa with different character of its bacterioviral infection in adolescents with chronic gastritis

Aim. To characterize the inflammatory process in gastric mucosa among adolescents with chronic gastritis in different variants of its bacterioviral infection.
 Materials and methods.Clinicoanamnestic, laboratory, endoscopic and morphological examination of 200 adolescents (age range 12–18 years) with chronic gastritis was carried out. In all patients, clinicoanamnestic data, standard laboratory study, esophagogastroduodenoscopy, gastrobiopsy followed by morphological analysis with visual analogue scale were assessed. According to the results of examination, all adolescents were divided into 4 groups depending on the character of bacterioviral infection of gastric mucosa.
 Results. No statistically significant differences were detected while comparing the rate of clinical manifestations of pain abdominal, dyspeptic, intoxication and asthenovegetative syndromes as well as changes, revealed in laboratory and ultrasound studies in the above mentioned groups of adolescents. Maximal presentation of macroscopic and pathohistological changes was registered in patients of group 4 (association between colonization of GM with highly pathogenic Hp strains and EBV persistence).
 Conclusions. The character of bacterioviral infection of gastric mucosa significantly determines the manifestation degree and activity of inflammatory process. The least degree of manifestation and activity of inflammatory process is registered when mucosa is colonized by low pathogenic Hp strains. Maximal presentation of macroscopic and pathohistological changes in the gastric mucosa is registered in adolescents with associated infection by high pathogenic Hp strains and Epstein-Barr virus. It is manifested by domination of marked and highly active inflammation and appearance of the signs of mucosal atrophy of gastric body and antrum.

Topical problems of chronic gastritis

The authors propose the definition of chronic gastritis with a brief overview of the history of investigation of this diseases and its prevalence with special reference to (1) the bacterial profile and its role in the development of infectious and inflammatory process in gastric mucosa, (2) the modern state of and new trends in the classification of chronic gastritis including their advantages and disadvantages, (3) the relationship between chronic gastritis and functional gastroduodenal dyspepsia syndrome. It is concluded that mucous microflora plays an important factor in the development ofpathology but H.pylori is not its predominant component. Modern classifications of chronic gastritis provide a basis for a deeper insight into evolution of chronic gastritis and its transformation into cancer. The diagnosis of ‘chronic gastritis with functional gastroduodenal dyspepsia syndrome‘ is invalid.

Tumor Suppresser Gene p53 Expression in Premalignant Lesions and Gastric Carcinoma - Prognostic Value

The aim of the study was to verify the presence of mutated tumor suppresser gene p53 in intestinal mucosa with histologically confirmed premalignant lesions and gastric carcinoma, and assess its prognostic value. The paper presents prospective study that included 50 patients with gastric adeno-carcinoma of intestinal type that were treated at Gastroenterohepatology Clinic, and 50 patients with histologically confirmed chronic atrophic H. pylori positive gastritis. In the mucosa biopsy samples, we analyzed presence, frequency and severity of inflammatory-regenerative, metaplastic and dysplastic changes. We typed intestinal metaplasia immunohistochemically and confirmed the presence of p53 onco-protein in antigen positive gastric carcinoma cells, and evaluated its prognostic value. Our results suggest that H. pylori acts as an initiator of inflammatory processes in gastric mucosa, which are followed by emergence of precancerous lesions. p53 is expressed late in carcinogenesis (14%) and as such, may be considered as an indicator of transformation of premalignant into malignant lesion.

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

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.

Induction of signal transduction pathways in rat gastric epithelial cells stimulated with interleukin-1beta.

Interleukin-1beta (IL-1beta) participates in cell growth, differentiation and apoptosis via activation of several kinases in a variety of cells. Mitogen-activated protein (MAP) kinases are important intermediates of the signal transduction pathway from the cell surface to the nucleus, leading to activation of transcription factors. There are no reports on the effect of IL-1beta on these pathways in gastric epithelial cells. To investigate whether IL-1beta activates MAP kinases [extracellular signal-regulated kinases (ERKs), c-Jun NH2-terminal kinases (JNKs) and p38 MAP kinase (p38 MAPK)] and nuclear factor (NF)-kappaB. a transcription factor, in gastric epithelial cells (RGM1). The activities of ERKs and JNKs were estimated by in-gel kinase assay, and p38 MAPK activity was measured by in vitro kinase assay at various time points (0-40 min) after addition of IL-1beta (100 pg/mL) for 20 min. The activity of NF-kappaB was analysed using gel mobility shift assay at times from 0 to 4 h after addition of IL-1beta. Activity of ERKs was detectable at 10 min, peaked at 20 min, and continued at increased levels until 40 min. Activity of both JNKs and p38 MAPK were detectable during 5-20 min, and then decreased within 40 min. Activation of NF-kappaB occurred at 30 min, and increased activity continued for 6 h. Interleukin-1beta activated MAP kinases and NF-kappaB in RGM1 cells. The activation induced by this cytokine may play an important role in the initiation of the inflammatory process in gastric mucosa.

Oxidant-induced activation of nuclear factor-kappa B in cultured guinea pig gastric epithelial cells.

The aim of this study was to reveal oxidant-sensitive components in gastric epithelial cells, which may regulate inflammatory processes in gastric mucosa. Gel mobility shift assay showed that treatment of cultured guinea pig gastric epithelial cells with hydrogen peroxide or diamide produced a KB oligonucleotide-protein complex within 5 min. The binding proteins consisted of a p50/p65 heterodimer, which was identified by immunosupershift, UV cross-linking, and immunoprecipitation analyses. Immunocytochemical study demonstrated that surface epithelial cells and parietal cells expressed p500 and p65 mainly in the cytosol, and the oxidants rapidly initiated the nuclear translocation of the components. The oxidants caused the up-regulation of p105 (a p50 precursor) synthesis and the expression of inducible nitric oxide synthase mRNA. These results suggest that the oxidant-sensitive p50/p65 heterodimer in gastric epithelial cells may play an important role in transcriptional activation of genes involved in inflammatory responses of the stomach.