1. ¹ Department of Microbiology, Daegu, Korea
2. ² Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea

Correspondence: Hee Sun Kim, MD, Department of Microbiology, College of Medicine, Yeungnam University, 317-1 Daemyungdong Namgu, Daegu, 705-717 Korea. Email: heesun@med.yu.ac.kr

Received 27 July 2004; Accepted 10 January 2005.

Abstract

15-Deoxy-^12,14-prostaglandin J₂ (15d-PGJ₂) was initially identified as a high affinity natural ligand for the peroxisome proliferator-activated receptor (PPAR)-. 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)-B-dependent transcription of inflammatory genes. In this study, we investigated the synergistic effect of 15d-PGJ₂ 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-PGJ₂ plus LPS simultaneously (15d-PGJ₂/LPS) showed similar patterns to the cells treated with LPS alone, and 15d-PGJ₂ had no effect on the stability of LPS-induced KC mRNA expression. Although NF-B activity in cells treated with LPS was augmented by 15d-PGJ₂, pyrrolidone dithiocarbamate (PDTC) did not block the synergistic effect of 15d-PGJ₂ on LPS-induced KC mRNA expression. However, the synergistic effect of 15d-PGJ₂ 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-PGJ₂ on the expression of LPS-induced KC mRNA in mouse peritoneal macrophages is possibly related to the MAPK signalling pathway, not to NF-B activation. These data may contribute to unravelling some of the different mechanisms contrary to the anti-inflammatory effect of 15d-PGJ₂.