Premium
Notch signaling modulates the activation of microglial cells
Author(s) -
Grandbarbe Luc,
Michelucci Alessandro,
Heurtaux Tony,
Hemmer Karin,
Morga Eleonora,
Heuschling Paul
Publication year - 2007
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20553
Subject(s) - notch signaling pathway , microbiology and biotechnology , biology , hes1 , microglia , hes3 signaling axis , transcription factor , signal transduction , nitric oxide , downregulation and upregulation , haematopoiesis , stat3 , effector , inflammation , immunology , stem cell , endocrinology , biochemistry , gene
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. © 2007 Wiley‐Liss, Inc.