PMID- 17130903 OWN - NLM STAT- MEDLINE DCOM- 20070522 LR - 20181201 IS - 0818-9641 (Print) IS - 0818-9641 (Linking) VI - 85 IP - 1 DP - 2007 Jan TI - Upregulation of MIP-2 (CXCL2) expression by 15-deoxy-Delta(12,14)-prostaglandin J(2) in mouse peritoneal macrophages. PG - 60-7 AB - A peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), has been reported to possess anti-inflammatory activity in activated monocytes/macrophages. In this study, we investigated the effect of 15d-PGJ(2) on the lipopolysaccharide (LPS)-induced expression of chemokine mRNAs, especially macrophage inhibitory protein (MIP)-2 (CXCL2), in mouse peritoneal macrophages. The inhibitory actions of the natural PPARgamma ligands, 15d-PGJ(2) and prostaglandin A1 (PGA1), on the expression of RANTES (regulated upon activation, normal T expressed and secreted; CCL5), MIP-1beta (CCL4), MIP-1alpha (CCL3), IFN-gamma-inducible protein 10 kilodaltons (IP-10; CXCL10) and monocyte chemoattractant protein-1 (MCP-1; CCL2) mRNA in LPS-treated cells were stronger than those of the synthetic PPARgamma ligands troglitazone and ciglitazone. However, 15d-PGJ(2) enhanced the expression of LPS-induced MIP-2 (CXCL2) mRNA. A specific PPARgamma antagonist (GW9662) had no effect on the inhibitory action of 15d-PGJ(2) and PGA1 in LPS-induced chemokine mRNA expression and on the synergistic action of 15d-PGJ(2) in LPS-induced MIP-2 (CXCL2) expression. Moreover, LPS itself reduced the expression of PPARgamma. Although the synergistic effect of 15d-PGJ(2) on LPS-induced MIP-2 (CXCL2) mRNA expression was remarkable, the production of MIP-2 (CXCL2) in cells treated with 15d-PGJ(2) and LPS did not increase compared to the production in cells treated with LPS alone. The synergistic action of 15d-PGJ(2) on LPS-induced MIP-2 (CXCL2) mRNA expression was dependent on the activation of nuclear factor-kappaB (NF-kappaB), and 15d-PGJ(2) increased the phosphorylation of p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in cells stimulated with LPS. These results suggest that the synergistic effect of 15d-PGJ(2) on LPS-induced MIP-2 (CXCL2) expression is PPARgamma-independent, and is mediated by the p38 and SAPK/JNK pathway in mitogen-activated protein kinase signaling pathways, which activates NF-kappaB. Our data may give more insights into the different mechanisms contrary to the anti-inflammatory effect of 15d-PGJ(2) on the expression of chemokine genes. FAU - Kim, Hyo Y AU - Kim HY AD - Department of Microbiology and Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, Korea. FAU - Kim, Hee S AU - Kim HS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061128 PL - United States TA - Immunol Cell Biol JT - Immunology and cell biology JID - 8706300 RN - 0 (15-deoxy-delta(12,14)-prostaglandin J2) RN - 0 (CXCL2 protein, human) RN - 0 (Chemokine CXCL2) RN - 0 (Chemokines) RN - 0 (Chemokines, CXC) RN - 0 (Chromans) RN - 0 (Immunologic Factors) RN - 0 (Ligands) RN - 0 (Lipopolysaccharides) RN - 0 (PPAR gamma) RN - 0 (Prostaglandins A) RN - 0 (RNA, Messenger) RN - 0 (Thiazolidinediones) RN - I66ZZ0ZN0E (Troglitazone) RN - RXY07S6CZ2 (Prostaglandin D2) RN - U8QXS1WU8G (ciglitazone) RN - VYR271N44P (prostaglandin A1) SB - IM MH - Animals MH - Cells, Cultured MH - Chemokine CXCL2 MH - Chemokines/metabolism MH - Chemokines, CXC/*metabolism MH - Chromans/pharmacology MH - Dose-Response Relationship, Drug MH - Immunologic Factors/*pharmacology MH - Ligands MH - Lipopolysaccharides/pharmacology MH - Macrophages, Peritoneal/drug effects/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - PPAR gamma/metabolism MH - Prostaglandin D2/*analogs & derivatives/pharmacology MH - Prostaglandins A/pharmacology MH - RNA, Messenger/metabolism MH - Thiazolidinediones/pharmacology MH - Troglitazone MH - *Up-Regulation EDAT- 2006/11/30 09:00 MHDA- 2007/05/23 09:00 CRDT- 2006/11/30 09:00 PHST- 2006/11/30 09:00 [pubmed] PHST- 2007/05/23 09:00 [medline] PHST- 2006/11/30 09:00 [entrez] AID - 7100001 [pii] AID - 10.1038/sj.icb.7100001 [doi] PST - ppublish SO - Immunol Cell Biol. 2007 Jan;85(1):60-7. doi: 10.1038/sj.icb.7100001. Epub 2006 Nov 28.