Cox-2 expression, PGE(2) and cytokines production are inhibited by endogenously synthesized n-3 PUFAs in inflamed colon of fat-1 mice

J Nutr Biochem. 2011 Apr;22(4):360-5. doi: 10.1016/j.jnutbio.2010.03.003. Epub 2010 Jul 23.


There is great interest in the role of polyunsaturated fatty acids (PUFAs) in promoting (n-6 class) or inhibiting (n-3 class) inflammation. Mammalian cells are devoid of desaturase that converts n-6 to n-3 PUFAs. Consequently, essential n-3 fatty acids must be supplied with the diet. We have studied the effect of endogenously produced n-3 PUFAs on colitis development in fat-1 transgenic mice carrying the Caenorhabditis elegans fat-1 gene encoding n-3 desaturase. Colonic cell lipid profile was measured by capillary gas chromatography in fat-1 and wild-type (WT) littermates fed standard diet supplemented with 10% (w/w) safflower oil rich (76%) in n-6 polyunsaturated linoleic acid (LA). Experimental colitis was induced by administrating 3% dextran sodium sulphate (DSS). Colitis was scored by histopatological analysis. Cyclooxygenase-2 (Cox-2) expression was evaluated by real time polymerase chain reaction. Prostaglandin E(2) (PGE(2)) levels and cytokine production were determined by enzyme and microsphere-based immunoassays, respectively. The n-6/n-3 PUFA ratios in colonic cells of fat-1 mice were markedly lower (9.83±2.62) compared to WT (54.5±9.24, P<.001). Results also showed an attenuation of colonic acute and chronic inflammation in fat-1 mice with significant decreases in PGE(2) production (P<.01) and Cox-2 expression (P<.01). High levels of colitis-induced proinflammatory cytokines, interleukin (IL)-18, IL-1α, IL-1β, IL-6, monocytes chemotactic proteins 1, 2 and 3 (MCP 1,2,3), matrix metalloproteinase 9 and tumor necrosis factor α (TNF-α) were down-regulated in DSS acutely and chronically treated fat-1 mice. The expression of fat-1 gene in the colon was associated with endogenous n-3 PUFAs production, decreased Cox-2 expression, increased PGE(2) and cytokine production.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins / genetics
  • Colitis / chemically induced
  • Colitis / metabolism*
  • Colitis / pathology
  • Colon / metabolism
  • Colon / pathology
  • Cyclooxygenase 2 / biosynthesis*
  • Cytokines / biosynthesis*
  • Dextran Sulfate
  • Dinoprostone / biosynthesis*
  • Fatty Acid Desaturases / genetics
  • Fatty Acids, Omega-3 / biosynthesis*
  • Fatty Acids, Unsaturated / pharmacology
  • Mice
  • Mice, Transgenic


  • Caenorhabditis elegans Proteins
  • Cytokines
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • fat-1 protein, C elegans
  • Dextran Sulfate
  • Fatty Acid Desaturases
  • Cyclooxygenase 2
  • Dinoprostone