Efeito da urease de Helicobacter pylori em células endoteliais

Abstract

The urease of Helicobacter pylori (HP) has been extensively reported as an important bacterial product which enables HP to colonize and survive in the stomach, favoring the occurrence of gastric ulcer and adenocarcinoma. Recently, we demonstrated that HP urease (HPU) has a pro-inflammatory effect on human neutrophils. Although the effects of HP on endothelial cells (EC) have been early described, the direct involvement of HPU in the vascular effects is not completely understood. This study aims to investigate the effects of HPU on EC and the signaling pathways involved in these processes. The treatment of EC with HPU (10nM) did not affect cell viability. On the other hand, HPU enhanced EC permeability and reduced transendothelial resistance. Corroborating these data, HPU caused dissociation of cell cell junctional cadherins, induced VE-cadherin phosphorylation, promoted alterations on the dynamics of actin cytoskeleton, and increased FAK phosphorylation. Additionally, HPU induced reactive oxygen species (ROS) and nitric oxide (NO) production, that were impaired by LY294002, a PI3K-AKT pathway inhibitor. HPU-induced ROS production activated nuclear factor κB (NF-kB). HPU also increased adhesion of neutrophils to EC and tubulogenesis,. The effects of HPU on EC are modulated by integrins, as they were attenuated in the presence of RGD peptides. Data presented here indicate that HPU activates EC, probably through an integrin-associated signaling, supporting its role as a pro-inflammatory and also pro-angiogenic key molecule in H pylori-related diseases.