title: Prostaglandin E2 stimulates granulocyte colony-stimulating factor production via the prostanoid EP2 receptor in mouse peritoneal neutrophils.
abstract: G-CSF is a hemopoietic growth factor involved in granulocytic differentiation of progenitor cells. In this study, we investigated the effects of PGE2 on G-CSF production in murine peritoneal neutrophils in vitro and in vivo. PGE2 augmented LPS-primed G-CSF release from peritoneal neutrophils. This augmentation was mimicked by a type E prostanoid receptor (EP)2-selective agonist but not by other EP-specific agonists. Indeed, the effect of PGE2 on G-CSF release was abolished in neutrophils isolated from EP2-deficient mice. PGE2 and an EP2 agonist have the ability to stimulate G-CSF gene expression even in the absence of LPS. In the casein-induced peritonitis model, the appearance of G-CSF in the casein-injected peritoneal cavity associated well with the timing of neutrophil infiltration as well as PGE2 levels in exudates, with a peak value at 6 h postinjection. Inhibition of endogenous PG synthesis by indomethacin resulted in a marked decrease in G-CSF content and neutrophil number in the peritoneal cavity. Moreover, EP2-deficient mice exhibited a strikingly reduced G-CSF content in peritoneal exudates with comparable responses in neutrophil migration and local PGE2 production at 6 h postinjection. These results suggest that the PGE2-EP2 system contributes to the local production of G-CSF during acute inflammation.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fukada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hana
authors.initials: H
authors.lastname: Yamane
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okuno
authors.forename: Katsuya
authors.initials: K
authors.lastname: Deai
authors.forename: Soken
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ichikawa
mesh_terms: D000818:Animals; D002364:Caseins / Q000633:toxicity; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D004357:Drug Synergism; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D002364:Caseins; D008070:Lipopolysaccharides; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D016179:Granulocyte Colony-Stimulating Factor; D000242:Cyclic AMP; D015232:Dinoprostone