Upregulation of MIP‐2 (CXCL2) expression by 15‐deoxy‐Δ12,14‐prostaglandin J2in mouse peritoneal macrophages
| Autor: | Hee S Kim, Hyo Young Kim |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Lipopolysaccharides
Chemokine CXCL2 Immunology Prostaglandin Ligands Mice Troglitazone chemistry.chemical_compound Downregulation and upregulation Animals Immunologic Factors Immunology and Allergy 15d pgj2 Macrophage RNA Messenger Chromans Cells Cultured Prostaglandins A Dose-Response Relationship Drug integumentary system Prostaglandin D2 Cell Biology Molecular biology Up-Regulation Mice Inbred C57BL PPAR gamma CXCL2 chemistry Macrophages Peritoneal 15 deoxy δ Thiazolidinediones Chemokines Chemokines CXC |
| Zdroj: | Immunology & Cell Biology. 85:60-67 |
| ISSN: | 1440-1711 0818-9641 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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