n-3 Fatty acids block TNF-α-stimulated MCP-1 expression in rat mesangial cells

• Published in: American journal of physiology. Renal physiology 2011-05, Vol.300 (5), p.F1142-F1151
• Main Authors: Diaz Encarnacion, Montserrat M, Warner, Gina M, Cheng, Jingfei, Gray, Catherine E, Nath, Karl A, Grande, Joseph P
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Binding Sites; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Docosahexaenoic Acids - pharmacology; Down-Regulation; Eicosapentaenoic Acid - pharmacology; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases - metabolism; Genes, Reporter; Humans; Male; Mesangial Cells - drug effects; Mesangial Cells - immunology; Mesangial Cells - metabolism; NF-kappa B - metabolism; Promoter Regions, Genetic - drug effects; Protein Kinase Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; Recombinant Proteins - metabolism; RNA, Messenger - metabolism; Transcription Factor AP-1 - metabolism; Transcriptional Activation - drug effects; Transfection; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00064.2011

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.