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PMID: 15498767 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A novel signaling pathway mediates the inhibition of CCL3/4 expression by prostaglandin E2.

The Journal of biological chemistry ·Vol. 279 ·No. 53 ·2004-12-31 ·Pages 55176-86

Jing H, Yen JH, Ganea D

Abstract

In response to pathogen-associated molecular patterns, dendritic cells initiate an innate immune response characterized by expression and release of proinflammatory cytokines and chemokines. The extent of the inflammatory response is limited by various endogenous factors, including lipid mediators such as prostaglandin E(2) (PGE(2)). We described previously the inhibitory effect of PGE(2) on the expression and release of the inflammatory chemokines CCL3 and CCL4 from activated dendritic cells. In this study we describe a novel PGE(2) signaling pathway that proceeds through EP-2 --> cAMP --> EPAC --> phosphatidylinositol 3-kinase --> protein kinase B --> GSK-3 and results in increased DNA binding of the CCAAT displacement protein (CDP), a potent mammalian transcriptional repressor. The direct link between CDP and CCL3/4 transcription was established in knock-down experiments using CDP small interference RNA.

MeSH Terms

Animals Bone Marrow Cells/metabolism CD11c Antigen/biosynthesis Cell Nucleus/metabolism Cell Separation Chemokine CCL3 Chemokine CCL4 Chemokines/antagonists & inhibitors,physiology Chemokines, CC/antagonists & inhibitors,biosynthesis Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism Cytokines/metabolism DNA/metabolism Dendritic Cells/metabolism Dinoprostone/metabolism Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Flow Cytometry Glycogen Synthase Kinase 3/metabolism Homeodomain Proteins Inflammation Lipid Metabolism Lipopolysaccharides/metabolism Macrophage Inflammatory Proteins/antagonists & inhibitors,biosynthesis Male Membrane Glycoproteins/metabolism Mice Mice, Inbred C57BL Models, Biological NF-kappa B/metabolism Nuclear Proteins/metabolism,physiology Phosphorylation Protein Binding Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-akt RNA, Small Interfering/metabolism Receptors, Cell Surface/metabolism Repressor Proteins/metabolism,physiology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Time Factors Toll-Like Receptors Transcription, Genetic

Chemicals

CD11c Antigen Ccl3 protein, mouse Ccl4 protein, mouse Chemokine CCL3 Chemokine CCL4 Chemokines Chemokines, CC Cux1 protein, mouse Cytokines Homeodomain Proteins Lipopolysaccharides Macrophage Inflammatory Proteins Membrane Glycoproteins NF-kappa B Nuclear Proteins Proto-Oncogene Proteins RNA, Small Interfering Receptors, Cell Surface Repressor Proteins Toll-Like Receptors DNA Cyclic AMP Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Cyclic AMP-Dependent Protein Kinases Glycogen Synthase Kinase 3 Dinoprostone

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Jing Huie

Department of Biological Sciences, Rutgers University, 101 Warren Street, Newark, NJ 07102, USA.

Yen Jui-Hung

Ganea Doina

Article Info

Journal

The Journal of biological chemistry

Abbr.

J Biol Chem

ISSN

0021-9258

DOI

10.1074/jbc.M409816200

Published

2004-12-31

Epub

2004-00-21

Pages

55176-86

Language

English

Region

United States

NLM ID

2985121R

Subset

Grants

NIAID NIH HHS · AI 47325 · United States

NIAID NIH HHS · AI 52306 · United States

External Links

PubMed source DOI: 10.1074/jbc.M409816200 View journal details

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A novel signaling pathway mediates the inhibition of CCL3/4 expression by prostaglandin E2.

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