Gobbetti, ThomasDalli, JesmondColas, RomainCanova, Donata FedericiAursnes, MariusBonnet, DelphineAlric, LaurentVergnolle, NathalieDeraison, CelineHansen, TrondSerhan, CharlesPerretti, Mauro2019-10-052017Gobbetti, Thomas, Jesmond Dalli, Romain A. Colas, Donata Federici Canova, Marius Aursnes, Delphine Bonnet, Laurent Alric, et al. 2017. “Protectin D1n-3 DPAand Resolvin D5n-3 DPAare Effectors of Intestinal Protection.” Proceedings of the National Academy of Sciences 114 (15): 3963–68. https://doi.org/10.1073/pnas.1617290114.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483499The 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 upregulation 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-alpha-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.en-USJournal Article2019-10-0510.1073/pnas.1617290114