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Upregulation of LPS‐induced chemokine KC expression by 15‐deoxy‐Δ 12,14 ‐prostaglandin J 2 in mouse peritoneal macrophages
Author(s) -
Kim Hyo Y,
Kim Hyun K,
Kim Jae R,
Kim Hee S
Publication year - 2005
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/j.1440-1711.2005.01329.x
Subject(s) - chemokine , mapk/erk pathway , downregulation and upregulation , chemistry , lipopolysaccharide , prostaglandin , messenger rna , kinase , proinflammatory cytokine , protein kinase a , receptor , microbiology and biotechnology , pharmacology , inflammation , biology , biochemistry , immunology , gene
15‐Deoxy‐Δ 12,14 ‐prostaglandin J 2 (15d‐PGJ 2 ) was initially identified as a high affinity natural ligand for the peroxisome proliferator‐activated receptor (PPAR)‐γ. 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)‐κB‐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‐κB 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‐κB activation. These data may contribute to unravelling some of the different mechanisms contrary to the anti‐inflammatory effect of 15d‐PGJ 2 .