Up-regulated microRNA-146a negatively modulate Helicobacter pylori-induced inflammatory response in human gastric epithelial cells

Microbes Infect. 2010 Oct;12(11):854-63. doi: 10.1016/j.micinf.2010.06.002. Epub 2010 Jun 11.

Abstract

Helicobacter pylori (H. pylori) is a major human pathogenic bacterium in gastric mucosa. However, the regulatory mechanism of H. pylori-induced immune response is not clear. MicroRNAs (miRNAs) have recently emerged as key post-transcriptional regulators of gene expression, and their role in H. pylori infection is just beginning to be explored. Here, we first reported that H. pylori infection up-regulated the expression of miR-146a in gastric epithelial cells as well as in gastric mucosal tissues in NF-κB-dependent manner. In turn, miR-146a may downregulate the expression of target genes, interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6). Furthermore, miR-146a negatively regulated H. pylori-triggered interleukin (IL)-8, growth-related oncogene (GRO)-α, and macrophage inflammatory protein (MIP) -3α through diminishing NF-κB activity. In conclusion, H. pylori-induced miR-146a plays a potential role in a negative feedback loop to modulate the inflammation by targeting IRAK1 and TRAF6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Epithelial Cells / immunology*
  • Epithelial Cells / microbiology
  • Female
  • Gastric Mucosa / pathology
  • Gene Expression Regulation*
  • Helicobacter pylori / immunology*
  • Humans
  • Inflammation*
  • Interleukin-1 Receptor-Associated Kinases / biosynthesis*
  • Male
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • NF-kappa B / biosynthesis
  • TNF Receptor-Associated Factor 6 / biosynthesis*

Substances

  • MIRN146 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • TNF Receptor-Associated Factor 6
  • Interleukin-1 Receptor-Associated Kinases