RRC ID 39766
Author Iwahashi H, Takeshita A, Hanazawa S.
Title Prostaglandin E2 stimulates AP-1-mediated CD14 expression in mouse macrophages via cyclic AMP-dependent protein kinase A.
Journal J Immunol
Abstract PGs play a functional role in the early stage of Gram-negative bacterial infections, because this prostanoid is produced rapidly by epithelial cells after a bacterial infection. CD14, one of the LPS receptors, is a key molecule in triggering the response to bacterial LPS in association with a Toll-like molecule. Therefore, in this study, we investigated the effect of PG on CD14 expression in mouse macrophages. PGE1, PGE2, and PGA1 among the PGs tested strongly stimulated the expression of the CD14 gene in the cells. The stimulatory action also was observed by Western blot analysis. cAMP-elevating agents stimulated expression of CD14 gene as well. Protein kinase A inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), but not protein kinase C inhibitor 3-(1-[3-(dimethylamino)propyl]-1H-indol-3-yl)-4-(1H-indol-3-yl)-1H-py rrole-2,5-dione (GF109203X), abolished the stimulated expression of CD14. A run-on assay showed that PGE2 stimulated the CD14 gene expression at the transcriptional level via protein kinase A. PGE2 also stimulated activation of AP-1, a heterodimer of c-Jun and c-Fos, because the prostanoid increased specific binding of nuclear proteins to the AP-1 consensus sequence and stimulated AP-1-promoted luciferase activity. PGE2-stimulated expression of CD14 was inhibited by antisense c-fos and c-jun oligonucleotides, but not by their sense oligonucleotides. Finally, PGE2 pretreatment synergistically stimulated LPS-induced expression of IL-1beta and IL-6 genes in mouse macrophages. Therefore, the present study demonstrates that PGE2 has the ability to stimulate AP-1-mediated expression of CD14 in mouse macrophages via cAMP-dependent protein kinase A.
Volume 164(10)
Pages 5403-8
Published 2000-5-15
DOI 10.4049/jimmunol.164.10.5403
PII ji_v164n10p5403
PMID 10799905
MeSH Animals Cell Line Colforsin / pharmacology Cyclic AMP / metabolism Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases / physiology* Dinoprostone / antagonists & inhibitors Dinoprostone / physiology* Drug Synergism Enzyme Inhibitors / pharmacology Gene Expression Regulation / drug effects Gene Expression Regulation / immunology Interleukin-1 / biosynthesis Interleukin-1 / genetics Interleukin-6 / biosynthesis Interleukin-6 / genetics Isoquinolines / pharmacology Lipopolysaccharide Receptors / biosynthesis* Lipopolysaccharide Receptors / genetics Lipopolysaccharides / pharmacology Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / enzymology* Macrophages, Peritoneal / immunology* Macrophages, Peritoneal / metabolism Mice Mice, Inbred BALB C Oligonucleotides, Antisense / pharmacology Prostaglandins / pharmacology Protein Kinase C / antagonists & inhibitors Proto-Oncogene Proteins c-fos / genetics Proto-Oncogene Proteins c-jun / genetics Sulfonamides* Transcription Factor AP-1 / metabolism Transcription Factor AP-1 / physiology* Transcription, Genetic / drug effects Transcription, Genetic / immunology
IF 4.886
Times Cited 29
Human and Animal Cells RAW 264(RCB0535)