期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 30, 页码 11276-11281出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0601280103
关键词
inflammation; inflammatory bowel disease; lipid mediators; resolvins; protectins
资金
- NIDCR NIH HHS [P50-DE016191, P50 DE016191] Funding Source: Medline
- NIDDK NIH HHS [DK43351, P30 DK040561-11, P30 DK040561, P30 DK043351] Funding Source: Medline
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 anti inflammatory 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 anti inflammatory 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-kappa B activity and expression of TNF alpha, inducible NO synthase, and IL-1 beta, with enhanced muco-protection probably because of the higher expression of trefoil factor 3, Toll-interacting protein, and zonula occludens-1. These results thus establish the fat-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.
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