CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2

Elke Scandella; Ying Men; Daniel F Legler; Silke Gillessen; Ladislav Prikler; Burkhard Ludewig; Marcus Groettrup

doi:10.1182/blood-2003-05-1643

CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2

Elke Scandella, Ying Men, Daniel F Legler, Silke Gillessen, Ladislav Prikler, Burkhard Ludewig, Marcus Groettrup

Division of Cancer Sciences (L5)

Cantonal Hospital, St. Gallen

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1595-1601
Number of pages	7
Journal	Blood
Volume	103
Issue number	5
DOIs	https://doi.org/10.1182/blood-2003-05-1643
Publication status	Published - 1 Mar 2004

Keywords

Blotting, Western
Calcium/metabolism
Cell Movement
Cells, Cultured
Chemokine CCL19
Chemokine CCL21
Chemokine CXCL12
Chemokines/metabolism
Chemokines, CC/metabolism
Chemokines, CXC/metabolism
Chemotaxis
Cyclic AMP-Dependent Protein Kinases/metabolism
Dendritic Cells/cytology
Dinoprostone/metabolism
Dose-Response Relationship, Drug
Egtazic Acid/analogs & derivatives
Humans
Ligands
Mitogen-Activated Protein Kinase 1/metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases/metabolism
Phosphatidylinositol 3-Kinases/metabolism
Phosphorylation
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins/metabolism
Proto-Oncogene Proteins c-akt
Receptors, CCR7
Receptors, Chemokine/metabolism
Signal Transduction
Time Factors
Type C Phospholipases/metabolism
Up-Regulation

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10.1182/blood-2003-05-1643

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title = "CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2",

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.",

keywords = "Blotting, Western, Calcium/metabolism, Cell Movement, Cells, Cultured, Chemokine CCL19, Chemokine CCL21, Chemokine CXCL12, Chemokines/metabolism, Chemokines, CC/metabolism, Chemokines, CXC/metabolism, Chemotaxis, Cyclic AMP-Dependent Protein Kinases/metabolism, Dendritic Cells/cytology, Dinoprostone/metabolism, Dose-Response Relationship, Drug, Egtazic Acid/analogs & derivatives, Humans, Ligands, Mitogen-Activated Protein Kinase 1/metabolism, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases/metabolism, Phosphatidylinositol 3-Kinases/metabolism, Phosphorylation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-akt, Receptors, CCR7, Receptors, Chemokine/metabolism, Signal Transduction, Time Factors, Type C Phospholipases/metabolism, Up-Regulation",

author = "Elke Scandella and Ying Men and Legler, {Daniel F} and Silke Gillessen and Ladislav Prikler and Burkhard Ludewig and Marcus Groettrup",

year = "2004",

month = mar,

day = "1",

doi = "10.1182/blood-2003-05-1643",

language = "English",

volume = "103",

pages = "1595--1601",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "5",

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TY - JOUR

T1 - CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2

AU - Scandella, Elke

AU - Men, Ying

AU - Legler, Daniel F

AU - Gillessen, Silke

AU - Prikler, Ladislav

AU - Ludewig, Burkhard

AU - Groettrup, Marcus

PY - 2004/3/1

Y1 - 2004/3/1

N2 - 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.

AB - 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.

KW - Blotting, Western

KW - Calcium/metabolism

KW - Cell Movement

KW - Cells, Cultured

KW - Chemokine CCL19

KW - Chemokine CCL21

KW - Chemokine CXCL12

KW - Chemokines/metabolism

KW - Chemokines, CC/metabolism

KW - Chemokines, CXC/metabolism

KW - Chemotaxis

KW - Cyclic AMP-Dependent Protein Kinases/metabolism

KW - Dendritic Cells/cytology

KW - Dinoprostone/metabolism

KW - Dose-Response Relationship, Drug

KW - Egtazic Acid/analogs & derivatives

KW - Humans

KW - Ligands

KW - Mitogen-Activated Protein Kinase 1/metabolism

KW - Mitogen-Activated Protein Kinase 3

KW - Mitogen-Activated Protein Kinases/metabolism

KW - Phosphatidylinositol 3-Kinases/metabolism

KW - Phosphorylation

KW - Protein-Serine-Threonine Kinases

KW - Proto-Oncogene Proteins/metabolism

KW - Proto-Oncogene Proteins c-akt

KW - Receptors, CCR7

KW - Receptors, Chemokine/metabolism

KW - Signal Transduction

KW - Time Factors

KW - Type C Phospholipases/metabolism

KW - Up-Regulation

U2 - 10.1182/blood-2003-05-1643

DO - 10.1182/blood-2003-05-1643

M3 - Article

C2 - 14592837

SN - 0006-4971

VL - 103

SP - 1595

EP - 1601

JO - Blood

JF - Blood

IS - 5

ER -

CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2

Abstract

Keywords

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