Helicobacter pylori (H.pylori) infection caused by gastric mucosal inflammation plays a pivotal role in the progression of gastric diseases. The recruitment and attachment of monocytes to the gastric mucosal epithelium are a major event in the early stages of H. pylori-associated gastric diseases. Everolimus is a mechanistic/mammalian target of rapamycin (mTOR) inhibitor used to prevent tumor growth by inhibiting the PI3K signaling pathway. Here, we examined the pharmacological role of Everolimus against H.pylori-induced damage in gastric epithelial cells. Firstly, we found that Everolimus ameliorated H.pylori-induced oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA). Secondly, Everolimus significantly reduced the expressions of the pro-inflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-8. Moreover, it decreased the production of the pro-inflammatory chemokines C-X-C motif ligand 1 (CXCL1) and macrophage chemoattractant protein-1 (MCP-1). Importantly, Everolimus suppressed the induction of the adhesion molecule intracellular adhesion molecule-1 (ICAM-1) and the attachment of THP-1 monocytes to gastric epithelial AGS cells. Our data also shows that Everolimus inhibited the activation of the NF-κB signaling pathway. Therefore, we conclude that Everolimus could protect gastric epithelial cells by mitigating H.pylori-induced inflammatory response and the attachment of monocytes to epithelial cells.
Keywords: Everolimus; Helicobacter pylori; NF-κB; gastritis; inflammation; monocyte attachment.