Abstract
15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) was initially identified as a high affinity natural ligand for the peroxisome proliferator-activated receptor (PPAR)-gamma. Recent studies have shown that it has a potent anti-inflammatory effect by attenuating the expression of proinflammatory mediators in activated macrophages, mainly through the inhibition of nuclear factor (NF)-kappaB-dependent transcription of inflammatory genes. In this study, we investigated the synergistic effect of 15d-PGJ(2) on the expression of LPS-induced chemokine KC mRNA in mouse peritoneal macrophages. The time course of KC mRNA expression in cells stimulated with 15d-PGJ(2) plus LPS simultaneously (15d-PGJ(2)/LPS) showed similar patterns to the cells treated with LPS alone, and 15d-PGJ(2) had no effect on the stability of LPS-induced KC mRNA expression. Although NF-kappaB activity in cells treated with LPS was augmented by 15d-PGJ(2), pyrrolidone dithiocarbamate (PDTC) did not block the synergistic effect of 15d-PGJ(2) on LPS-induced KC mRNA expression. However, the synergistic effect of 15d-PGJ(2) was markedly inhibited when the macrophages were treated with a inhibitor of the mitogen-activated protein kinase (MAPK) signalling pathway, 2'-amino-3'-methoxyflavine (PD98059). Therefore, the mechanism of synergistic action of 15d-PGJ(2) on the expression of LPS-induced KC mRNA in mouse peritoneal macrophages is possibly related to the MAPK signalling pathway, not to NF-kappaB activation. These data may contribute to unravelling some of the different mechanisms contrary to the anti-inflammatory effect of 15d-PGJ(2).
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Blotting, Northern
-
Chemokine CXCL1
-
Chemokines, CXC / genetics*
-
Cycloheximide / pharmacology
-
Dactinomycin / pharmacology
-
Dose-Response Relationship, Drug
-
Drug Synergism
-
Enzyme Inhibitors / pharmacology
-
Flavonoids / pharmacology
-
Gene Expression / drug effects
-
Hypoglycemic Agents / pharmacology
-
Immunologic Factors / pharmacology
-
Intercellular Signaling Peptides and Proteins / genetics*
-
Lipopolysaccharides / pharmacology*
-
Macrophages, Peritoneal / drug effects*
-
Macrophages, Peritoneal / metabolism
-
Mice
-
Mice, Inbred C57BL
-
Mitogen-Activated Protein Kinases / antagonists & inhibitors
-
Mitogen-Activated Protein Kinases / metabolism
-
NF-kappa B / antagonists & inhibitors
-
NF-kappa B / metabolism
-
PPAR gamma / genetics
-
Prostaglandin D2 / analogs & derivatives*
-
Prostaglandin D2 / pharmacology
-
Pyrrolidines / pharmacology
-
RNA Stability / drug effects
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Specific Pathogen-Free Organisms
-
Thiazolidinediones / pharmacology
-
Thiocarbamates / pharmacology
-
Time Factors
-
Up-Regulation / drug effects
-
Up-Regulation / genetics
Substances
-
15-deoxy-delta(12,14)-prostaglandin J2
-
Chemokine CXCL1
-
Chemokines, CXC
-
Cxcl1 protein, mouse
-
Enzyme Inhibitors
-
Flavonoids
-
Hypoglycemic Agents
-
Immunologic Factors
-
Intercellular Signaling Peptides and Proteins
-
Lipopolysaccharides
-
NF-kappa B
-
PPAR gamma
-
Pyrrolidines
-
RNA, Messenger
-
Thiazolidinediones
-
Thiocarbamates
-
lipopolysaccharide, Escherichia coli O111 B4
-
Dactinomycin
-
pyrrolidine dithiocarbamic acid
-
Cycloheximide
-
Mitogen-Activated Protein Kinases
-
Prostaglandin D2
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
-
ciglitazone