title: Upregulation of LPS-induced chemokine KC expression by 15-deoxy-delta12,14-prostaglandin J2 in mouse peritoneal macrophages.
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).
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Korea.
authors.forename: Hyo Y
authors.initials: HY
authors.lastname: Kim
authors.forename: Hyun K
authors.initials: HK
authors.lastname: Kim
authors.forename: Jae R
authors.initials: JR
authors.lastname: Kim
authors.forename: Hee S
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D045162:Thiazolidinediones / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007004:Hypoglycemic Agents; D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D011759:Pyrrolidines; D012333:RNA, Messenger; D045162:Thiazolidinediones; D013859:Thiocarbamates; C440499:lipopolysaccharide, Escherichia coli O111 B4; D003609:Dactinomycin; C020972:pyrrolidine dithiocarbamic acid; D003513:Cycloheximide; D020928:Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; C039671:ciglitazone