Jagged1 regulates the activation of astrocytes via modulation of NFκB and JAK/STAT/SOCS pathways

Eleonora Morga*, Laila Mouad-Amazzal, Paul Felten, Tony Heurtaux, Mike Moro, Alessandro Michelucci, Sebastien Gabel, Luc Grandbarbe, Paul Heuschling

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)


The Notch pathway is implicated in many aspects of the central nervous system (CNS) development and functions. Recently, we and others identified the Notch pathway to be involved in inflammatory events of the CNS. To understand the implication of this pathway on astrocytes, we have studied the Jagged-Notch-Hes pathway under inflammatory conditions. LPS exposure induced an upregulation of Jagged1 expression on cultured astrocytes. To address the role of Jagged1 in the modulation of inflammation, we used a siRNA mediated silencing of Jagged1 (siRNA J1). Jagged1 inhibition induced important variations on the Notch pathway components like Hes1, Hes5, Notch3, and RBP-Jκ. siRNA J1 repressed the mRNA expression of genes known as hallmarks of the gliosis like GFAP and endothelin(B) receptor. On activated astrocytes, the inhibition of Jagged1 had antiinflammatory effects and resulted in a decrease of LPS-induced proinflammatory cytokines (IL1β, IL1α, and TNFα) as well as the iNOS expression. The inhibition of Jagged1 induced a modulation of the JAK/STAT/SOCS signaling pathway. Most interestingly, the siRNA J1 decreased the LPS-induced translocation of NFκB p65 and this could be correlated to the phosphorylation of IκBα. These results suggest that during inflammatory and gliotic events of the CNS, Jagged1/Notch signaling sustains the inflammation mainly through NFκB and in part through JAK/STAT/SOCS signaling pathways.

Original languageEnglish
Pages (from-to)1741-1753
Number of pages13
Issue number16
Publication statusPublished - 2009
Externally publishedYes


  • Gliosis
  • Hes1
  • Inflammation
  • Notch


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