Cox-2 expression, PGE2 and cytokines production are inhibited by endogenously synthesized n-3 PUFAs in inflamed colon of fat-1 mice Journal Article

Authors: Gravaghi, C.; La Perle, K. M. D.; Ogrodwski, P.; Kang, J. X.; Quimby, F.; Lipkin, M.; Lamprecht, S. A.
Article Title: Cox-2 expression, PGE2 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 E2 (PGE2) 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 PGE2 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 PGE2 and cytokine production. © 2011 Elsevier Inc.
Keywords: controlled study; protein expression; unclassified drug; histopathology; nonhuman; animal cell; mouse; mammalia; animal tissue; mus; gene expression; gelatinase b; interleukin 1beta; animal experiment; animal model; inflammation; diet supplementation; transgenic mouse; mus musculus; enzyme immunoassay; tumor necrosis factor alpha; protein synthesis; cyclooxygenase 2; prostaglandin e2; interleukin 6; colitis; cytokine production; real time polymerase chain reaction; omega 3 fatty acid; caenorhabditis elegans; monocyte chemotactic protein 3; interleukin 1alpha; intestine cell; monocyte chemotactic protein 1; interleukin 18; microsphere; cox-2; fat-1 mice; acyl coenzyme a desaturase; dextran derivative; dextran sodium sulphate; monocyte chemotactic protein 2; omega 6 fatty acid; safflower oil; capillary gas chromatography; carthamus tinctorius
Journal Title: Journal of Nutritional Biochemistry
Volume: 22
Issue: 4
ISSN: 0955-2863
Publisher: Elsevier Inc.  
Date Published: 2011-04-01
Start Page: 360
End Page: 365
Language: English
DOI: 10.1016/j.jnutbio.2010.03.003
PROVIDER: scopus
PUBMED: 20655721
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 23 June 2011" - "CODEN: JNBIE" - "Source: Scopus"
Citation Impact
MSK Authors