Proteinase-Activated Receptor-2 Mediates the Expression of Integrin α5 and β1 in Helicobacter pylori-Infected Gastric Epithelial AGS Cells

Abstract

Background/Aim: Proteinase-activated receptor-2 (PAR2), which is activated by trypsin, is known to be associated with expression of adhesion molecule integrins. We previously demonstrated that Helicobacter pylori induced the expression of integrin α₅ and β₁ in human gastric epithelial cells. The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of PAR2, which mediates the expression of integrin α₅ and β₁ and thus cell adhesion to fibronectin in gastric epithelial AGS cells. Methods and Results: mRNA expressions of PAR2, trypsinogen 1 and 2, and integrin α₅ and β₁ were assessed by RT-PCR analysis while protein levels of PAR2, trypsin as well as integrin α₅ and β₁ were determined by Western blot analysis. The activity of trypsin in the medium was determined by fluorometric analysis. Cell adhesion assay was performed colorimetrically. H. pylori induced the expressions of PAR2 and integrin α₅ and β₁ of the cells. H. pylori increased mRNA expression of trypsinogen 1 and 2 as well as the level and activity of trypsin in the medium. H. pylori induced cell adhesion to fibronectin. H. pylori-induced expression of integrin α₅ and β₁ and adhesion of the cells to fibronectin were inhibited in the cells transfected with PAR2 antisense oligonucleotide or treated with a soybean trypsin inhibitor, anti-integrin α₅ antibody or β₁ antibody. Conclusion:H. pylori induces the expression of integrin α₅ and β₁ and adhesion of the cells to fibronectin through PAR2 which is induced and may be activated by trypsin in H. pylori-infected gastric epithelial cells. PAR2 may have an important role in gastric cell adhesion and possibly carcinogenesis associated with H. pylori.