MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells

Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2735-40. doi: 10.1073/pnas.0811073106. Epub 2009 Feb 4.

Abstract

In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Base Sequence
  • Cells, Cultured
  • DNA Primers
  • Dendritic Cells / metabolism*
  • Humans
  • Interleukin-1 / metabolism*
  • Lymphocyte Activation
  • MicroRNAs / physiology*
  • Monocytes / metabolism*
  • RNA Processing, Post-Transcriptional
  • Signal Transduction / physiology*
  • Toll-Like Receptors / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA Primers
  • Interleukin-1
  • MicroRNAs
  • TAB2 protein, human
  • Toll-Like Receptors

Associated data

  • GEO/GSE13296