n-3 Fatty acids block TNF-α-stimulated MCP-1 expression in rat mesangial cells
| Autor: | Montserrat M. Diaz Encarnacion, Joseph P. Grande, Jingfei Cheng, Catherine E. Gray, Gina M. Warner, Karl A. Nath |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Transcriptional Activation MAPK/ERK pathway medicine.medical_specialty Docosahexaenoic Acids Physiology Anti-Inflammatory Agents Down-Regulation Biology Transfection Rats Sprague-Dawley Genes Reporter Internal medicine medicine Animals Humans RNA Messenger Northern blot Extracellular Signal-Regulated MAP Kinases Promoter Regions Genetic Protein Kinase Inhibitors Cells Cultured Chemokine CCL2 Unsaturated fatty acid Binding Sites Mesangial cell Tumor Necrosis Factor-alpha NF-kappa B Articles Fish oil Eicosapentaenoic acid Recombinant Proteins Rats Enzyme Activation Transcription Factor AP-1 Endocrinology Eicosapentaenoic Acid Docosahexaenoic acid Mesangial Cells |
| Zdroj: | American Journal of Physiology-Renal Physiology. 300:F1142-F1151 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00064.2011 |
| Popis: | Monocyte chemoattractant protein 1 (MCP-1) is a CC cytokine that fundamentally contributes to the pathogenesis of inflammatory renal disease. MCP-1 is highly expressed in cytokine-stimulated mesangial cells in vitro and following glomerular injury in vivo. Interventions to limit MCP-1 expression are commonly effective in assorted experimental models. Fish oil, an abundant source of n-3 fatty acids, has anti-inflammatory properties, the basis of which remains incompletely defined. We examined potential mechanisms whereby fish oil reduces MCP-1 expression and thereby suppresses inflammatory responses to tissue injury. Cultured mesangial cells were treated with TNF-α in the presence of the n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA); equimolar concentrations of the n-6 fatty acids LA and OA served as controls. MCP-1 mRNA expression was assessed by Northern blotting, and transcriptional activity of the MCP-1 promoter was assessed by transient transfection. The involvement of the ERK and NF-κB pathways was evaluated through transfection analysis and the use of the MEK inhibitor U0126. DHA and EPA decreased TNF-α-stimulated MCP-1 mRNA expression by decreasing transcription of the MCP-1 gene. DHA and EPA decreased p-ERK expression and nuclear translocation of NF-κB, both of which are necessary for TNF-α-stimulated MCP-1 expression. Both NF-κB and AP-1 sites were involved in transcriptional regulation of the MCP-1 gene by DHA and EPA. We conclude that DHA and EPA inhibit TNF-α-stimulated transcription of the MCP-1 gene through interaction of signaling pathways involving ERK and NF-κB. We speculate that such effects may contribute to the salutary effect of fish oil in renal and vascular disease. |
| Databáze: | OpenAIRE |
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