Differential Role of ERK and p38 on NF- κ B Activation in Helicobacter pylori-Infected Gastric Epithelial Cells.

Abstract

Gastric cancer, as well as inflammation, caused by Helicobacter pylori, activates the production of chemokines by activation of redox-sensitive transcription factor NF-κB in gastric epithelial cells. Mitogen-activated protein kinases including extracellular signal-regulated kinase (ERK) and p38 kinase (p38) are activated by Helicobacter pylori, which may regulate NF-κB activation in the infected cells. However the mechanisms how ERK and p38 induce NF-κB activation have not been investigated. Present study aims to investigate the role of ERK and p38 on the activation of NF-κB in Helicobacter pylori-infected AGS cells. Western blot analysis was performed for determining the levels of IκB, p105, p50 and p65 in gastric epithelial cells infected with Helicobacter pylori and treated with ERK inhibitor U0126 and p38 inhibitor SB203580. Helicobacter pylori induced the degradation of IκBα and upregulation of p105, p50 and p65 in the infected cells. U0126 inhibited the degradation of IκBα while SB203580 suppressed expression of p105, p50 and p65 in Helicobacter pylori-infected cells. ERK and p38 differentially activate NF-κB; ERK induces degradation of IκBα while p38 upregulates the expression of p50 and p65, subunits of NF-κB in Helicobacter pylori-infected gastric epithelial AGS cells.