Notch signaling modulates the activation of microglial cells.
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.
Grandbarbe
Luc
L
Department of Life Sciences, University of Luxembourg, Luxembourg.
Michelucci
Alessandro
A
Heurtaux
Tony
T
Hemmer
Karin
K
Morga
Eleonora
E
Heuschling
Paul
P
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D017628:Microglia / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010587:Phagocytosis / Q000502:physiology; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051881:Receptor, Notch1 / Q000235:genetics* / Q000502:physiology*; D051880:Receptors, Notch / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha
D015850:Interleukin-6; C497763:Notch1 protein, rat; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D051880:Receptors, Notch; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide