CCR7-specific migration to CCL19 and CCL21 is induced by PGE(2) stimulation in human monocytes: Involvement of EP(2)/EP(4) receptors activation

Autor: Sandra C. Côté, Nancy Dumais, Salim Bounou, Stamatoula Pasvanis
Rok vydání: 2008
Předmět:
medicine.medical_specialty
Chemokine
Receptors
CCR7
Time Factors
medicine.medical_treatment
Prostaglandin E2 receptor
p38 mitogen-activated protein kinases
Immunology
Blotting
Western
Gene Expression
Stimulation
Biology
CD16
Dinoprostone
Monocytes
Cell Movement
Internal medicine
Cell Line
Tumor
medicine
Cyclic AMP
Humans
Receptors
Prostaglandin E
Receptor
Promoter Regions
Genetic
Molecular Biology
Transcription factor
Cells
Cultured
Chemokine CCL21
Dose-Response Relationship
Drug
Reverse Transcriptase Polymerase Chain Reaction
Nuclear Proteins
Receptors
Prostaglandin E
EP2 Subtype
Flow Cytometry
Cyclic AMP-Dependent Protein Kinases
Cell biology
Endocrinology
biology.protein
Chemokine CCL19
lipids (amino acids
peptides
and proteins)
Receptors
Prostaglandin E
EP4 Subtype
Prostaglandin E
Protein Binding
Zdroj: Molecular immunology. 46(13)
ISSN: 1872-9142
Popis: The recent demonstration that newly recruited monocytes do not die at the site of inflammation, but migrate to draining lymph nodes, raises the question on the mechanism involved in this process. In this study, we demonstrate for the first time that prostaglandin E(2) (PGE(2)) regulates the expression and the activity of CCR7 in human blood-isolated monocytes as well as in the MONO-MAC-1 cell lineage. PGE(2) induces intracellular cAMP formation through engagement of the E-prostanoid 2/E-prostanoid 4 (EP(2)/EP(4)) receptors present on monocytes. Migration to chemokines CCL19 and CCL21 in the PGE(2)-stimulated monocytes is mediated through the augmentation of cAMP concentration and furthermore, the cAMP/PKA pathway appears to act as the major inducer of CCR7 transcription in MONO-MAC-1. While p38 MAPK was induced by PGE(2), we observed that PGE(2) can downregulate p42/p44 MAPK phosphorylation. At the transcription level, inhibition of p38 MAPK inhibits CCR7 mRNA expression. Finally, we demonstrated that transcription factors CREB-1 and C/EBPalpha and C/EBPbeta are translocated to the nucleus following PGE(2) stimulation and bind the potent CCR7 promoter region. Our findings may have important implication for HIV-1 migration to the lymph nodes since macrophages and monocytes, particularly CD16 positive subset, are susceptible to HIV-1 infection.
Databáze: OpenAIRE
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