Open AccessTransgenic mice rich in endogenous omega-3 fatty acids are protected from colitis
Author(s) -
Christian A. Hudert,
Karsten H. Weylandt,
Yan Lü,
Jingdong Wang,
Song Hong,
Axel Dignaß,
Charles N. Serhan,
Jing Kang
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0601280103
Subject(s) - polyunsaturated fatty acid , inflammation , lipid signaling , eicosanoid , proinflammatory cytokine , leukotriene b4 , chemistry , genetically modified mouse , colitis , transgene , endogeny , prostaglandin e2 , biochemistry , biology , pharmacology , arachidonic acid , endocrinology , immunology , enzyme , fatty acid , gene
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are the precursors of potent lipid mediators and play an important role in regulation of inflammation. Generally, n-6 PUFA promote inflammation whereas n-3 PUFA have antiinflammatory properties, traditionally attributed to their ability to inhibit the formation of n-6 PUFA-derived proinflammatory eicosanoids. Newly discovered resolvins and protectins are potent antiinflammatory lipid mediators derived directly from n-3 PUFA with distinct pathways of action. However, the role of the n-3 PUFA tissue status in the formation of these antiinflammatory mediators has not been addressed. Here we show that an increased n-3 PUFA tissue status in transgenic mice that endogenously biosynthesize n-3 PUFA from n-6 PUFA leads to significant formation of antiinflammatory resolvins and effective reduction in inflammation and tissue injury in colitis. The endogenous increase in n-3 PUFA and related products did not decrease n-6 PUFA-derived lipid mediators such as leukotriene B4 and prostaglandin E2. The observed inflammation protection might result from decreased NF-κB activity and expression of TNFα, inducible NO synthase, and IL-1β, with enhanced mucoprotection probably because of the higher expression of trefoil factor 3, Toll-interacting protein, and zonula occludens-1. These results thus establish thefat-1 transgenic mouse as a new experimental model for the study of n-3 PUFA-derived lipid mediators. They add insight into the molecular mechanisms of inflammation protection afforded by n-3 PUFA through formation of resolvins and protectins other than inhibition of n-6 PUFA-derived eicosanoid formation.