Molecular and Immunopathological Role of Nuclear Factor K B Detected By Insitu Hybridization in Pathogenesis of Chronic Atrophic Gastritis in Iraqi Patients

Abstract

Chronic Atrophic gastritis (CAG) is a histopathological entity characterized by chronic inflammation of the gastric mucosa with loss of gastric glandular cells and replacement by intestinal-type epithelium and fibrous tissue. Atrophy of the gastric mucosa is the endpoint of chronic processes, such as chronic gastritis associated with Helicobacter pylori infection. This study designed to determine the molecular role of NFkB signaling on Fas receptor mediated apoptosis in H.pylori associated CAG cases. Forty five patients suffering from CAG that proved via endoscopical and histopathological examination were eligible for this study. Males represent (73.33%) and the rest (26.67%) were females with a mean age of 39.26 years .twenty apparently healthy volunteers (10 male and 10 female) with the mean age 38 years and age range (23-58) years were enrolled as control group. Multiple mucosal biopsy specimens were taken from the inflamed area of gastric mucosa for rapid urease test other biopsy specimens were fixed with 10% buffered formalin for preparation of paraffin embedded tissue blocks to prepare slides for histological examination using haematoxylin-eosin stain to evaluate the grades of Polymorphonuclear leukocytes(PMNs) and lymphocytes infiltration . Insitu hybridization technique (ISH) using biotinylated long DNA probe for human NF-KB Gene and for human FAS gene as well as H.pylori Cag A gene were used for detection of NF-KB and Fas mRNA and Cag A mRNA expression in tissue infiltrated lymphocytes and neutrophils as well as gastric epithelial cells and for detection of H.pylori Cag A. This study explained that there was a statistical significant positive linear relationship between lymphocytes grade and Fas mRNA expression in PMNs and gastric epithelial cells. PMN grade has significant positive linear relationship with each of the following markers: Tissue Fas mRNA expression. Tissue NFkB mRNA expression, lymphocytes NFkB mRNA expression, PMN NFkB mRNA expression, Cag A mRNA expression. Lymphocytes Fas mRNA expression has significant positive linear relationship with PMN Fas mRNA expression and Cag A mRNA expression .PMN Fas mRNA expression has significant positive linear relationship with Cag A mRNA expression and negative linear relationship with tissue NFkB mRNA expression . Tissue Fas mRNA expression has significant positive linear relationship with tissue NFkB mRNA expression ; lymphocytes NFkB mRNA expression ; PMN NFkB mRNA expression ;Cag A mRNA expression . Tissue NFKB mRNA expression has significant positive linear relationship with lymphocytes NFkB mRNA expression; PMN NFkB mRNA expression. Lymphocytes NFkB mRNA expression has significant positive linear relationship with PMN NFkB mRNA expression. This study conclude that NFkB play a vital role in determination of immunopathological and inflammatory events of gastritis that leads finally to development of atrophic changes