Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response

J Infect Dis. 2009 Sep 15;200(6):916-25. doi: 10.1086/605443.


Background: MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at posttranscriptional level. H. pylori is a major human pathogenic bacterium in gastric mucosa. To date, the role of miRNAs in response to H. pylori infection has not been explored.

Methods: The expression profile of cellular miRNAs during H. pylori infection was analyzed by using microarray and quantitative reverse-transcriptase polymerase chain reaction. The potential target of miR-155 was identified by luciferase assay and Western blot. Promoter analysis and inhibitor experiment were used to investigate the pathway involved in the induction of miR-155. Examination of miR-155 function was performed by overexpression and inhibition of miR-155.

Results: H. pylori was able to increase the miR-155 expression in gastric epithelial cell lines and gastric mucosal tissues, and nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) pathway were required for the induction of miR-155. miR-155 may down-regulate IkappaB kinase epsilon, Sma- and Mad-related protein 2 (SMAD2), and Fas-associated death domain protein. Furthermore, the overexpression of miR-155 negatively regulated the release of interleukin-8 and growth-related oncogene-alpha.

Conclusions: This study provides the first description of increased expression of miR-155 in H. pylori infection, and miR-155 may function as novel negative regulator that help to fine-tune the inflammation response of H. pylori infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chemokine CXCL1 / metabolism
  • Fas-Associated Death Domain Protein / metabolism
  • Female
  • Gastric Mucosa / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori*
  • Humans
  • I-kappa B Kinase / metabolism
  • Inflammation / metabolism*
  • Interleukin-8 / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Smad2 Protein / metabolism


  • CXCL1 protein, human
  • Chemokine CXCL1
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Interleukin-8
  • MIRN155 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • SMAD2 protein, human
  • Smad2 Protein
  • I-kappa B Kinase