Molecular and Immunopathological Role of Gastric Versus lymphocytes Interleukin 8 Gene Expression in H.pylori Induced Fas-Fasl Apoptotic Pathway in Gastroduodenal Ulcer in Iraqi Patients

Abstract

The main Objective was to determine the role of Cag A positive H.pylori in modulation of expression of FAS,FASL and IL8 mRNA in gastroduodenal tissue and infiltrated lymphocytes and its effects in development of gastroduodenal ulcer (GDU).Twenty one GDU patients and (10) control were chosen. Multiple gastric mucosal biopsies taken for rapid urease test and slides preparation from paraffin blocks. Biotinylated DNA probe for human FAS, FASL and IL8, genes used for detection of their expression in tissue lymphocytes and gastric epithelial cells using ISH technique. Biotinylated DNA probe for H.pylori Cag A gene used for detection of its expression in gastric epithelial cells. Insitu CagA was detected in (42.85%) of GDU cases. The toxin was not detected among control. There is a highly significant differences among CagA positive cases as well as Cag Anegative cases in FAS mRNA, FasL mRNA and IL8 mRNA expression between Gastroduodenal tissue(GDT) and Tissue infiltrating lymphocytes( TILs)(p <0.05).Significant difference in tissue FAS mRNA and tissue IL8 mRNA over expression (p<0.05) was detected. while no such difference was detected in tissue FASL mRNA between CagA positive and CagA negative cases was detected. Significant difference in TILs FasL and TILs IL8 mRNA expression between Cag A positive and Cag A negative GDU cases (p<0.05) .while no such difference in expression of FAS m RNA in TILs between Cag Apositive and CagA negative GDU cases . Significant difference between control group and H.pylori Cag positive GDU cases (P<0.05) as well as H.pylori CagAnegative cases (p< 0.05 ) was detected.in normal control gastroduodenal tissue , Fas mRNA, FasL mRNA and IL8 mRNA expressed in less than 5% of infiltrated Lymphocytes which considered negative. Lymphocytes FAS mRNA expression has significant correlation with tissue FAS (r= 0.435 , p=0.049). Tissue Fas mRNA expression has significant correlation with Lymphocytes FASL (r= 0. 561 , p=0.008);Lymphocytes IL8 (r= 0. 529 , p=0.014) and CagA (r= 0.436, p=0.048). Lymphocytes FASL mRNA expression has significant correlation with Lymphocytes IL8 (r= 0.650, p=0.001) . In conclusions Cag A gene play a vital role in modulation of FAS , FASL and IL8 genes expressed in gastroduodenal ulcer tissue and infiltrated lymphocytes which reflect the severity of histopathological changes during the course of H.pylori infection. Keywords: gastroduodenal ulcer, Fas, FasL, ,IL8 ,H.pylori ,Cag A ,Iraq