Protectin D1 _{n-3 DPA} and resolvin D5 _{n-3 DPA} are effectors of intestinal protection

Abstract

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 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-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.inflammation resolution | specialized proresolving mediators | omega-3 fatty acids | intravital microscopy | neutrophils

Crosstalk Between the Gut Microbiome and Bioactive Lipids: Therapeutic Targets in Cognitive Frailty

“…In the context of inflammatory bowel disease, systemic treatment with ω-3 DPA-derived protectin D1 and ω-3 DPAderived resolvin D5 protected against colitis and intestinal ischemia/reperfusion-induced inflammation in mice (101). In contrast, the inhibition of the activity of 15-lipoxygenase-one of the enzymes that mediates the synthesis of DPA-derived protectin D1-reduced the production of this anti-inflammatory SPM and, in turn, increased intestinal inflammation (101). These innovative strategies may be used to promote anti-inflammatory and tissue-protective effects in gut inflammatory disorders.…”

Resolvin E1 attenuates inj ury‐induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration

“…BLT1 is abundantly expressed by polymorphonuclear neutrophils (PMNs), whereas ChemR23 is expressed by macrophages and dendritic cells, although it can also be expressed by VSMCs and platelets (15,16). Notably, RvE1 has been shown to possess protective properties in a number of inflammatory-disease animal models, including peritonitis (8), colitis (17), polymicrobial sepsis (18,19), airway inflammation (20)(21)(22), acute kidney injury (23), asthma (22), and myocardial infarction (24). Previous studies have also demonstrated that fish oil intake (mainly containing EPA and docosahexaenoic acid) can suppress balloon injury-induced arterial neointima formation in animals (25).…”

Plant‐ and Fish‐Derived n‐3 PUFAs Suppress Citrobacter Rodentium–Induced Colonic Inflammation

“…Given the role that omega‐3 fatty acid‐derived specialized pro‐resolving mediators play in the resolution of colonic inflammation, we next investigated whether FSO, AO, and FO regulated the concentrations of these molecules during colonic inflammation. In colon samples, we identified mediators from all four major fatty acid metabolomes in accordance with published criteria . Using Partial Least Square Discriminant Analysis, which generates a regression model based on concentrations of lipid mediators that are differently expressed between two groups, we found that each of the three supplement groups gave a distinct lipid cluster from mice given SO ( Figure 2 A).…”