Notch signaling modulates the activation of microglial cells

Luc Grandbarbe, Alessandro Michelucci, Tony Heurtaux, Karin Hemmer, Eleonora Morga, Paul Heuschling*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

68 Citations (Scopus)

Abstract

The Notch signaling pathway plays a crucial role in specifying cellular fate in metazoan development by regulating communication between adjacent cells. Correlative studies suggested an involvement of Notch in hematopoietic cell development. Here, we report that the Notch pathway is expressed and active in microglial cells. During inflammatory activation, the transcription of the Notch down-stream effector Hes1 is downregulated. When Notch1 transcription in microglia is inhibited, an upregulation of the expression of pro-inflammatory cytokines is observed. Notch stimulation in activated microglia, using a soluble form of its ligand Jagged1, induces a decrease in pro-inflammatory cytokines secretion and nitric oxide production as well as an increase in phagocytic activity. Notch-stimulation is accompanied by an increase in the rate of STAT3 phosphorylation and nuclear translocation. Our results show that the Notch pathway plays an important role in the control of inflammatory reactions in the CNS.

Original languageEnglish
Pages (from-to)1519-1530
Number of pages12
JournalGLIA
Volume55
Issue number15
DOIs
Publication statusPublished - 15 Nov 2007
Externally publishedYes

Keywords

  • Hes1
  • Jagged1
  • Nitric oxide
  • Pro-inflammatory cytokines
  • STAT3

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