TGF-beta induces the expression of the FLICE-inhibitory protein and inhibits Fas-mediated apoptosis of microglia

Détails

ID Serval
serval:BIB_46E2700BC58B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TGF-beta induces the expression of the FLICE-inhibitory protein and inhibits Fas-mediated apoptosis of microglia
Périodique
European Journal of Immunology
Auteur(s)
Schlapbach  R., Spanaus  K. S., Malipiero  U., Lens  S., Tasinato  A., Tschopp  J., Fontana  A.
ISSN
0014-2980 (Print)
Statut éditorial
Publié
Date de publication
12/2000
Volume
30
Numéro
12
Pages
3680-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Résumé
During inflammatory reactions in the central nervous system (CNS), resident macrophages, the microglia, are exposed to Th1 cell-derived cytokines and pro-apoptotic Fas ligand (FasL). Despite the presence of TNF-alpha and IFN-gamma, both being capable of sensitizing microglia to FasL, apoptosis of microglia is not a hallmark of inflammatory diseases of the CNS. In the present study, TGF-beta is found to counteract the effect of TNF-alpha and IFN-gamma to sensitize microglia to FasL-mediated apoptosis. Resistance to Fas-mediated apoptosis by TGF-beta does not correlate with a down-regulation of Fas expression. As a key inhibitor of Fas-mediated apoptosis, we found expression of the cellular FLICE-inhibitory protein (c-FLIP) to be induced by TGF-beta in resting as well as in activated microglia. Induction of FLIP was found to depend on a mitogen-activated protein kinase kinase (MKK)-dependent pathway as shown by the use of the specific MKK-inhibitor PD98059. The presence of FLIP strongly interfered with FasL-induced activation of caspase-8 and caspase-3 preventing subsequent cell death. The presented data provide the first evidence for a TGF-beta-mediated FLIP in macrophage-like cells and suggest a mode of action for the anti-apoptotic role of TGF-beta in the CNS.
Mots-clé
Animals Antigens, CD95/*physiology Apoptosis/*drug effects Caspase 3 Caspase 8 Caspase 9 Caspases/*antagonists & inhibitors Fas Ligand Protein Membrane Glycoproteins/pharmacology Mice Mice, Inbred C57BL Microglia/drug effects/*physiology Transforming Growth Factor beta/*pharmacology
Pubmed
Web of science
Création de la notice
24/01/2008 16:18
Dernière modification de la notice
03/03/2018 16:48
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