PMID- 15266020
OWN - NLM
STAT- MEDLINE
DCOM- 20040830
LR  - 20220309
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 66
IP  - 2
DP  - 2004 Aug
TI  - Prostaglandin E2 inhibits the phospholipase D pathway stimulated by 
      formyl-methionyl-leucyl-phenylalanine in human neutrophils. Involvement of EP2 
      receptors and phosphatidylinositol 3-kinase gamma.
PG  - 293-301
AB  - Prostaglandin E(2) (PGE(2)), originally discovered as a pro-inflammatory 
      mediator, also inhibits several chemoattractant-elicited neutrophil functions, 
      including adhesion, secretion of cytotoxic enzymes, production of superoxide 
      anions, and chemotaxis. In this study, we have examined the effects of PGE(2) and 
      prostaglandin E (EP) receptor-selective agonists/antagonists on several steps of 
      the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced phospholipase D (PLD) 
      activation pathway in human neutrophils to elucidate the PGE(2) inhibitory 
      mechanism. PGE(2) and EP(2) receptor agonists inhibited the stimulation of the 
      activity of PLD induced by fMLP in a concentration-dependent manner. The 
      fMLP-stimulated translocation to membranes of protein kinase C alpha, Rho, and 
      Arf GTPases was diminished in the presence of PGE(2) or EP(2) agonists. Moreover, 
      PGE(2) and EP(2) agonists decreased the activation of phosphatidylinositol 
      3-kinase gamma (PI3Kgamma) and Tec kinases as well as the tyrosine 
      phosphorylation of proteins stimulated by fMLP. These data provide strong 
      evidence that 1) the inhibitory effects of PGE(2) on the fMLP-induced PLD 
      activation pathway were mediated via EP(2) receptors and that 2) the suppression 
      of PI3Kgamma activity was the crucial step in the EP(2)-mediated inhibition of 
      the fMLP-induced signaling cascade.
FAU - Burelout, Chantal
AU  - Burelout C
AD  - Centre de Recherche en Rhumatologie-Immunologie, Pavillon CHUL, Canada.
FAU - Thibault, Nathalie
AU  - Thibault N
FAU - Levasseur, Sylvain
AU  - Levasseur S
FAU - Simard, Sebastien
AU  - Simard S
FAU - Naccache, Paul H
AU  - Naccache PH
FAU - Bourgoin, Sylvain G
AU  - Bourgoin SG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Isoenzymes)
RN  - 0 (PTGER2 protein, human)
RN  - 0 (Receptors, Prostaglandin E)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 42HK56048U (Tyrosine)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 59881-08-2 (methionyl-leucyl-phenylalanine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class Ib Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.137 (PIK3CG protein, human)
RN  - EC 2.7.11.13 (PRKCA protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factor 1)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - ADP-Ribosylation Factor 1/metabolism
MH  - Calcium/metabolism
MH  - Cell Membrane/drug effects/metabolism
MH  - Class Ib Phosphatidylinositol 3-Kinase
MH  - Dinoprostone/*pharmacology
MH  - Humans
MH  - Isoenzymes/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/*analogs & derivatives/antagonists & 
      inhibitors/*pharmacology
MH  - Neutrophils/*drug effects/enzymology/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phospholipase D/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Kinase C/metabolism
MH  - Protein Kinase C-alpha
MH  - Receptors, Prostaglandin E/*metabolism
MH  - Receptors, Prostaglandin E, EP2 Subtype
MH  - Tyrosine/metabolism
MH  - rho GTP-Binding Proteins/metabolism
EDAT- 2004/07/22 05:00
MHDA- 2004/08/31 05:00
CRDT- 2004/07/22 05:00
PHST- 2004/07/22 05:00 [pubmed]
PHST- 2004/08/31 05:00 [medline]
PHST- 2004/07/22 05:00 [entrez]
AID - 66/2/293 [pii]
AID - 10.1124/mol.66.2.293 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2004 Aug;66(2):293-301. doi: 10.1124/mol.66.2.293.