Abstract
The control of dendritic cell (DC) migration is pivotal for the initiation of cellular immune responses. When activated with inflammatory stimuli, the chemokine receptor CCR7 is up-regulated on DCs. Activated DCs home to lymphoid organs, where the CCR7 ligands CCL19 and CCL21 are expressed. We previously found that human monocyte-derived DCs (MoDCs) exclusively migrated to CCL19 and CCL21 when matured in the presence of prostaglandin (PG) E2. Because PGE2 did not alter CCR7 cell surface expression, we examined whether PGE2 may exert its effect by coupling CCR7 to signal transduction modules. Indeed, stimulation with CCR7 ligands led to enhanced phosphatidylinositol-3-kinase-mediated phosphorylation of protein kinase B when MoDCs were matured in the presence of PGE2. Moreover, CCL19/CCL21-induced intracellular calcium mobilization in MoDCs occurred only when PGE2 was present during maturation. MoDC migration to CCL19 and CCL21 was dependent on phospholipase C and intracellular calcium flux but not on phosphatidylinositol-3 kinase. Hence, our data provide insight into CCL19/CCL21-triggered signal transduction pathways and identify a novel function for PGE2 in controlling the migration of mature MoDCs by facilitating CCR7 signal transduction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Calcium / metabolism
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Cell Movement
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Cells, Cultured
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Chemokine CCL19
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Chemokine CCL21
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Chemokine CXCL12
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Chemokines / metabolism
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Chemokines, CC / metabolism
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Chemokines, CC / physiology*
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Chemokines, CXC / metabolism
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Chemotaxis
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dendritic Cells / cytology*
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Dinoprostone / metabolism
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Dinoprostone / physiology*
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Dose-Response Relationship, Drug
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Egtazic Acid / analogs & derivatives*
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Egtazic Acid / pharmacology
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Humans
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Ligands
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Receptors, CCR7
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Receptors, Chemokine / metabolism
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Signal Transduction
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Time Factors
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Type C Phospholipases / metabolism
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Up-Regulation
Substances
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CCL19 protein, human
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CCL21 protein, human
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CCR7 protein, human
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CXCL12 protein, human
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Chemokine CCL19
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Chemokine CCL21
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Chemokine CXCL12
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Chemokines
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Chemokines, CC
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Chemokines, CXC
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Ligands
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Proto-Oncogene Proteins
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Receptors, CCR7
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Receptors, Chemokine
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Egtazic Acid
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Type C Phospholipases
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Dinoprostone
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Calcium