IL-22 negatively regulates Helicobacter pylori-induced CCL20 expression in gastric epithelial cells
Journal
PLoS ONE
Journal Volume
9
Journal Issue
5
Date Issued
2014
Author(s)
Abstract
Helicobacter pylori is a Gram-negative bacterium that infects the human gastric mucosa and causes various gastric diseases. H. pylori infection induces the production of inflammatory chemokine CCL20 in gastric mucosa and leads to gastric inflammation. Given that the IL-22/IL-22R axis plays a critical role in the regulation of homeostasis and inflammation of epithelial cells at barrier surfaces, we investigated the effect of IL-22 on CCL20 expression induced by H. pylori. We demonstrated that H. pylori infection of the gastric epithelia-derived AGS cells significantly induced CCL20 expression and the induction was inhibited by IL-22. Functional analysis of the CCL20 promoter revealed that the H. pylori-induced CCL20 expression required the activation of NF-κB, and that IL-22 inhibited the induction by attenuating NF-κB activation. Knockdown of endogenous STAT3 by either short interfering RNAs or a short hairpin RNA significantly reduced the inhibitory effect of IL-22. Furthermore, STAT3 phosphorylation elicited by IL-22 was crucial for the inhibition of H. pyloriinduced CCL20 expression. Consistent with the in vitro data showing that IL-22 negatively regulated H. pylori-induced CCL20 expression in gastric epithelial cells, studies on the tissue sections from patients with H. pylori infection also revealed an inverse association of IL-22 expression and CCL20 expression in vivo. Together, our findings suggest that IL-22 plays a role in the control of overproduction of the inflammatory chemokine and thus may protect the gastric mucosa from inflammation-mediated damage. ? 2014 Chen et al.
SDGs
Other Subjects
I kappa B; immunoglobulin enhancer binding protein; interleukin 22; macrophage inflammatory protein 3alpha; short hairpin RNA; small interfering RNA; STAT3 protein; CCL20 protein, human; immunoglobulin enhancer binding protein; interleukin derivative; interleukin-22; luciferase; macrophage inflammatory protein 3alpha; primer DNA; STAT3 protein; STAT3 protein, human; article; binding site; controlled study; gene silencing; Helicobacter infection; Helicobacter pylori; human; human cell; human tissue; immunity; marginal zone lymphoma; nonhuman; promoter region; protein expression; protein phosphorylation; signal transduction; stomach epithelium; transcription regulation; antagonists and inhibitors; chromatin immunoprecipitation; drug effects; enzyme linked immunosorbent assay; gel mobility shift assay; genetics; Helicobacter pylori; immunohistochemistry; metabolism; microbiology; phosphorylation; real time polymerase chain reaction; RNA interference; stomach mucosa; Western blotting; Blotting, Western; Chemokine CCL20; Chromatin Immunoprecipitation; DNA Primers; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Helicobacter pylori; Humans; Immunohistochemistry; Interleukins; Luciferases; NF-kappa B; Phosphorylation; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; RNA Interference; STAT3 Transcription Factor
Publisher
Public Library of Science
Type
journal article