Nephrol Dial Transplant (2004) 19: 312-319
© ERA–EDTA 2004; all rights reserved
Original Article
Dexamethasone regulates AP-1 to repress TNF-
induced MCP-1 production in human glomerular endothelial cells
1Department of Internal Medicine, 2Department of Urology and 3Department of Biochemistry, Asan Medical Center, College of Medicine, University of Ulsan, Seoul and 4Department of Internal Medicine, Keimyung University School of Medicine, Taegue, Korea
Correspondence and offprint requests to: Su-Kil Park, MD, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea. Email: skpark{at}www.amc.seoul.kr
Background. Glomerular endothelial cells play a role in the pathogenesis of glomerulonephritis by producing chemotactic factors. We investigated the role of NF-
B and AP-1 in tumour necrosis factor 
(TNF-) induced monocyte chemoattractant protein 1 (MCP-1) production in cultured human glomerular endothelial cells (HGEC). We also examined whether or not these processes could be modified by glucocorticoid.
Methods. MCP-1 protein and mRNA levels were measured by ELISA and northern blot. NF-B and AP-1 binding activity were assessed by electrophoretic mobility shift assay. Cytosolic IB and nuclear p65 protein were evaluated by western blot. For specific inhibition of NF-B or AP-1, we used a decoy oligodeoxynucleotide.
Results. TNF- (10 ng/ml) increased MCP-1 mRNA expression in HGEC and also the release of MCP-1 protein into culture media. These effects could be partially inhibited by dexamethasone (10 nM). TNF- induced MCP-1 production appeared to be NF-B and AP-1 interdependent, based on the following results. (i) TNF- increased NF-B and AP-1 binding activity. (ii) Both NF-B decoy oligodeoxynucleotide and AP-1 decoy oligodeoxynucleotide partially suppressed TNF- induced MCP-1 mRNA expression. On the other hand, dexamethasone decreased TNF- induced DNA-binding activity of AP-1 without an effect on the DNA-binding activity of NF-B, cytosolic IB degradation or p65 nuclear translocation.
Conclusions. These data demonstrate that while TNF- induced MCP-1 production is mediated by the cooperative action of NF-B and AP-1 in HGEC, dexamethasone represses TNF- induced MCP-1 production via suppression of AP-1 binding activity.
Keywords: AP-1; decoy oligonucleotide; dexamethasone; endothelial cells; MCP-1; NF-B
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