title: Cox-2 expression, PGE(2) and cytokines production are inhibited by endogenously synthesized n-3 PUFAs in inflamed colon of fat-1 mice.
abstract: 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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA. cgravaghi@strang.org
authors.forename: Claudia
authors.initials: C
authors.lastname: Gravaghi
authors.forename: Krista M D
authors.initials: KM
authors.lastname: La Perle
authors.forename: Paul
authors.initials: P
authors.lastname: Ogrodwski
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.forename: Fred
authors.initials: F
authors.lastname: Quimby
authors.forename: Martin
authors.initials: M
authors.lastname: Lipkin
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lamprecht
mesh_terms: D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000096:biosynthesis*; D044943:Fatty Acid Desaturases / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D029742:Caenorhabditis elegans Proteins; D016207:Cytokines; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; C466741:fat-1 protein, C elegans; D016264:Dextran Sulfate; D044943:Fatty Acid Desaturases; D051546:Cyclooxygenase 2; D015232:Dinoprostone