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标题：Protectin D1n-3 DPA and resolvin D5n-3 DPA are effectors of intestinal protection
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作者：Thomas Gobbetti ; Jesmond Dalli ; Romain A. Colas 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：15
页码：3963-3968
DOI：10.1073/pnas.1617290114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The resolution of inflammation is an active process orchestrated by specialized proresolving lipid mediators (SPM) that limit the host response within the affected tissue; failure of effective resolution may lead to tissue injury. Because persistence of inflammatory signals is a main feature of chronic inflammatory conditions, including inflammatory bowel diseases (IBDs), herein we investigate expression and functions of SPM in intestinal inflammation. Targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was used to identify SPMs from n-3 polyunsaturated fatty acids in human IBD colon biopsies, quantifying a significant up-regulation of the resolvin and protectin pathway compared with normal gut tissue. Systemic treatment with protectin (PD)1_{n-3 DPA} or resolvin (Rv)D5_{n-3 DPA} protected against colitis and intestinal ischemia/reperfusion-induced inflammation in mice. Inhibition of 15-lipoxygenase activity reduced PD1_{n-3 DPA} and augmented intestinal inflammation in experimental colitis. Intravital microscopy of mouse mesenteric venules demonstrated that PD1_{n-3 DPA} and RvD5_{n-3 DPA} decreased the extent of leukocyte adhesion and emigration following ischemia-reperfusion. These data were translated by assessing human neutrophil–endothelial interactions under flow: PD1_{n-3 DPA} and RvD5_{n-3 DPA} reduced cell adhesion onto TNF-α–activated human endothelial monolayers. In conclusion, we propose that innovative therapies based on n-3 DPA-derived mediators could be developed to enable antiinflammatory and tissue protective effects in inflammatory pathologies of the gut.
关键词：inflammation resolution ; specialized proresolving mediators ; omega-3 fatty acids ; intravital microscopy ; neutrophils