4.8 Article

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

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0811073106

关键词

bic/miR-155; LPS; TAB2; TLR/IL-1 pathway

资金

  1. Ministere de la Recherche et de la Technologie
  2. Reseau National Genopole
  3. La Ligue Nationale Contre le Cancer and the Human Frontier of Science Program
  4. Swiss National Science Foundation
  5. European Molecular Biology Organization Young Investigators
  6. DC-THERA Network of Excellence

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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.

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