GSK-3 mediates differentiation and activation of proinflammatory dendritic cells
The key components of the intracellular molecular network required for the expression of a specific function of dendritic cells (DCs) are as yet undefined. Using an in vitro model of human monocyte-derived DC differentiation, this study investigates the role of glycogen synthase kinase 3 (GSK-3), a...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[15 February 2007]
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| In: |
Blood
Year: 2007, Volume: 109, Issue: 4, Pages: 1584-1592 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2006-06-028951 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2006-06-028951 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006497120420014 
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| Author Notes: | Elena Rodionova, Michael Conzelmann, Eugene Maraskovsky, Michael Hess, Michael Kirsch, Thomas Giese, Anthony D. Ho, Margot Zöller, Peter Dreger, Thomas Luft |
MARC
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| 245 | 1 | 0 | |a GSK-3 mediates differentiation and activation of proinflammatory dendritic cells |c Elena Rodionova, Michael Conzelmann, Eugene Maraskovsky, Michael Hess, Michael Kirsch, Thomas Giese, Anthony D. Ho, Margot Zöller, Peter Dreger, Thomas Luft |
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| 520 | |a The key components of the intracellular molecular network required for the expression of a specific function of dendritic cells (DCs) are as yet undefined. Using an in vitro model of human monocyte-derived DC differentiation, this study investigates the role of glycogen synthase kinase 3 (GSK-3), a multifunctional enzyme critical for cellular differentiation, apoptosis, self-renewal, and motility, in this context. We demonstrate that GSK-3 (1) inhibits macrophage development during differentiation of DCs, (2) is constitutively active in immature DCs and suppresses spontaneous maturation, and (3) acquires a proinflammatory functional status mediating high levels of IL-12, IL-6, and TNF-α secretion, and partially inhibits IL-10 in the context of DC activation. In particular, GSK-3 enhances IL-12p35 mRNA expression and thus the production of the proinflammatory cytokine IL-12p70 by integrating the activities of other kinases priming GSK-3 targets and the inhibitory effects of Akt-1. GSK-3 may therefore act as a key integrator of activating and inhibitory pathways involved in proinflammatory DC differentiation and activation. | ||
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