Work

A Novel Signaling Pathway Mediates the Inhibition of CCL3/4 Expression by Prostaglandin E2

Year: 2004
Type: article
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.
Language: English
Subfield: Pharmacology
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1979998554
FWCI: 3.127
Cites: 39
Cited by: 82
Related to: 10