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

Montserrat M. Diaz Encarnacion, Gina M. Warner, Jingfei Cheng, Catherine E. Gray, Karl A. Nath, Joseph P. Grande

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Monocyte chemoattractant protein1 (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-kB pathways was evaluated through transfection analysis and the use of the MEK inhibitor U0126. DHA and EPA decreased TNF-alpha;- 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-kB, both of which are necessary for TNF-α-stimulated MCP-1 expression. Both NF-kB 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-kB. We speculate that such effects may contribute to the salutary effect of fish oil in renal and vascular disease.

Original languageEnglish (US)
Pages (from-to)1142-1151
Number of pages10
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Fish oil
  • Inflammation
  • Transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Urology

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