title: Prostaglandin E2 stimulates AP-1-mediated CD14 expression in mouse macrophages via cyclic AMP-dependent protein kinase A.
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.
authors.affiliation: Department of Oral Microbiology, Meikai University School of Dentistry, Keyakidai, Sakado City, Saitama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Iwahashi
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
authors.forename: S
authors.initials: S
authors.lastname: Hanazawa
mesh_terms: D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000502:physiology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D013449:Sulfonamides; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology
chemical_list: D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D007546:Isoquinolines; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016376:Oligonucleotides, Antisense; D011453:Prostaglandins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D013449:Sulfonamides; D018808:Transcription Factor AP-1; D005576:Colforsin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide