Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • DKFZ Publication Database  (2)
  • CELL  (2)
Collection
  • DKFZ Publication Database  (2)
  • 1
    Keywords: APOPTOSIS ; CELLS ; EXPRESSION ; IN-VITRO ; CELL ; Germany ; human ; INHIBITION ; KINASE ; MODEL ; PATHWAY ; PATHWAYS ; VITRO ; COMPONENTS ; DIFFERENTIATION ; ACTIVATION ; DENDRITIC CELLS ; PHOSPHORYLATION ; SCHIZOPHRENIA ; TARGET ; COMPONENT ; MODULATION ; beta-catenin ; TARGETS ; HIGH-LEVEL ; secretion ; SYNTHASE ; development ; CYTOKINE PRODUCTION ; LEVEL ; ENZYME ; GLYCOGEN-SYNTHASE KINASE-3 ; function ; depression ; INHIBIT ; BIPOLAR DISORDER ; LITHIUM TREATMENT
    Abstract: 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-alpha 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
    Type of Publication: Journal article published
    PubMed ID: 17032918
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: CELLS ; EXPRESSION ; CELL ; Germany ; KINASE ; MODEL ; PATHWAY ; PATHWAYS ; VOLUME ; DEATH ; transcription ; NF-KAPPA-B ; ACTIVATION ; LIGAND ; INDUCTION ; CONTRAST ; DENDRITIC CELLS ; LYMPH-NODES ; SIGNAL ; FORM ; DIFFERENCE ; CELL-DEATH ; SIGNALING PATHWAYS ; MIGRATION ; ONCOGENE ; ATHEROSCLEROSIS ; immune response ; IMMUNE-RESPONSE ; PERIPHERAL-BLOOD ; CD4(+) T-CELLS ; F ; AUTOIMMUNITY ; CYTOKINE ; PERSISTENT ; NODES ; RE ; STRENGTH ; CD40 LIGAND ; CD40-CD40 LIGAND ; IL-12 PRODUCTION ; PHYSIOLOGICAL STIMULI
    Abstract: Migration to lymph nodes and secretion of cytokines are critical functions of mature dendritic cells (DCs); however, these 2 functions are not necessarily linked. This is the first report showing that quantitative differences in identical signaling pathways determine DC migration and cytokine secretion. Using different polymerized forms of CD40 ligand, we demonstrate that the strength and persistence of CD40 signaling can induce either function. Induction of monocyte-derived DC (MoDC) migration required a weak and transient CD40 signal, whereas strong and persistent CD40 signaling blocked migration and biased toward cytokine secretion. In contrast to MoDCs, CD40 activation of CD1c(+) peripheral blood DCs (PBDCs) induced a nonpersistent, intracellular signaling profile resulting in migratory-type DCs unable to secrete interleukin-12p70 (IL-12p70). Extracellular signal-regulated kinase 1/2 (ERK1/2) and p38K activation synergistically mediated cytokine secretion, whereas migration was enhanced by p38K activation but reduced by persistent ERK1/2 activity. This model of signal strength and persistence also applied when stimulating DCs with intact microbes. Thus, a novel concept emerges in which the type of immune response induced by DCs is tuned by the strength and persistence of DC activating signals. (C) 2004 by The American Society of Hematology
    Type of Publication: Journal article published
    PubMed ID: 15113760
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...