resolvin-d5 and Inflammation

Resolvin D5 (RvD5), 7S,17S-dihydroxy-4Z,8E,10Z,13Z,15E,19Z-docosahexaenoic acid (DHA) is a specialized pro-resolving mediator (SPM) generated in human macrophages. It is implicated in the resolution of inflammation and synthesized using an inefficient chemical process. Here, DHA-enriched oil hydrolysate was prepared from oils by lipase with resin treatment and solvent extraction. The reaction factors on the biotransformation of oil hydrolysate into RvD5 were optimized using Escherichia coli expressing arachidonate double-oxygenating 15S-lipoxygenase. After optimization, the cells converted 5.0 mM (1.64 g/L) DHA in oil hydrolysate into 4.0 mM (1.44 g/L) RvD5 in a bioreactor for 3.0 h, which was 15-fold higher than that in a flask before optimization, and RvD5 with a purity of > 97% was prepared from reaction solution by treatments of resins. This is the first trial for the production of C22-dihydroxy fatty acid using a bioreactor. This study will contribute to the large-scale production of SPMs from oils.

Topics: Bioreactors; Docosahexaenoic Acids; Escherichia coli; Humans; Inflammation; Lipoxygenases

Resolvins (RvD1, RvD2 and RvE1) are endogenous anti-inflammatory lipid mediators that display potent analgesic properties in somatic pain by modulating transient receptor potential vanilloid 1 (TRPV1) activation. To what extent these molecules could also have a beneficial effect on TRPV1 sensitisation and visceral hypersensitivity (VHS), mechanisms involved in IBS, remains unknown.. The effect of RvD1, RvD2 and RvE1 on TRPV1 activation and sensitisation by histamine or IBS supernatants was assessed on murine dorsal root ganglion (DRG) neurons using live Ca. RvD1, RvD2 and RvE1 prevented histamine-induced TRPV1 sensitisation in DRG neurons at doses devoid of an analgesic effect. Of note, RvD2 also reversed TRPV1 sensitisation by histamine and IBS supernatant. This effect was blocked by the G protein receptor 18 (GPR18) antagonist O-1918 (3-30 µM) and by pertussis toxin. In addition, RvD2 reduced the capsaicin-induced Ca. Our data suggest that RvD2 and GPR18 agonists may represent interesting novel compounds to be further evaluated as treatment for IBS.

Topics: Adult; Animals; Capsaicin; Disease Models, Animal; Docosahexaenoic Acids; Eicosapentaenoic Acid; Enterobacteriaceae Infections; Female; Ganglia, Spinal; Histamine; Humans; Hypersensitivity; Inflammation; Irritable Bowel Syndrome; Male; Mice; Middle Aged; Neurons; Rats; Receptors, Cannabinoid; TRPV Cation Channels

Resolvins, are specialized pro-resolving mediators (SPMs) derived from n-3 polyunsaturated fatty acids. They contribute actively to the resolution of inflammation, but little is known concerning their role in chronic inflammation, such as in rheumatoid arthritis (RA). Here, we performed lipid mediator (LM) profiling in tissues from the paws of SKG arthritic mice using lipid chromatography (LC)/mass spectrometry (MS)/MS-based LM metabololipidomics. We found elevated levels of SPMs including resolvin D5 (RvD5) in these tissues. Moreover, RvD5 levels were significantly correlated with arthritis disease activity. From experiments to assess the role of RvD5 in the pathology of RA, we concluded that RvD5 suppressed Th17 cell differentiation and facilitated regulatory T cell differentiation, as well as inhibiting CD4

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Differentiation; Cell Proliferation; Chromatography, High Pressure Liquid; Docosahexaenoic Acids; Foot; Humans; Inflammation; Mice; Osteogenesis; Tandem Mass Spectrometry; Th17 Cells; Zymosan

One of the omega-3 essential fatty acids, docosahexaenoic acid (DHA), is a significant constituent of the cell membrane and the precursor of several potent lipid mediators. These mediators are considered to be important in preventing or treating several diseases. Resolvin D5, an oxidized lipid mediator derived from DHA, has been known to exert anti-inflammatory effects. However, the detailed mechanism underlying these effects has not yet been elucidated in human monocytic THP-1 cells. In the present study, we investigated the effects of resolvin D5 on inflammation-related signaling pathways, including the extracellular signal-regulated kinase (ERK)-nuclear factor (NF)-κB signaling pathway. Resolvin D5 downregulated the production of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 (CCL5). Additionally, these inhibitory effects were found to be modulated by mitogen-activated protein kinase (MAPK) and NF-κB in lipopolysaccharide (LPS)-treated THP-1 cells. Resolvin D5 inhibited the LPS-stimulated phosphorylation of ERK and translocation of p65 and p50 into the nucleus, resulting in the inhibition of IL-6 and CCL5 production. These results revealed that resolvin D5 exerts anti-inflammatory effects in LPS-treated THP-1 cells by regulating the phosphorylation of ERK and nuclear translocation of NF-kappaB.

Topics: Anti-Inflammatory Agents; Cell Survival; Chemokine CCL5; Docosahexaenoic Acids; Down-Regulation; Humans; Inflammation; Interleukin-6; Lipopolysaccharides; MAP Kinase Signaling System; Monocytes; Phosphorylation; Signal Transduction; THP-1 Cells

The mechanisms that drive programmed resolution of inflammation remain elusive. Here, we report the temporal regulation of soluble (s) and transmembrane (m) fibrinogen-like protein 2 (Fgl2) during inflammation and show that both sFgl2 and mFgl2 correlate with the outcome. The expression and ectodomain shedding of Fgl2 are respectively promoted by miR-466l and metalloproteinases (ADAM10 and ADAM17) during inflammation resolution. Deficiency of Fgl2 enhances polymorphonuclear neutrophil (PMN) infiltration but impairs macrophage (MΦ) maturation and phagocytosis and inhibits the production of n-3 docosapentaenoic acid-derived resolvin 5 (RvDp5). In contrast, administration of sFgl2 blunts PMN infiltration as well as promotes PMN apoptosis and RvDp5 biosynthesis. By activating ALX/FPR2, RvDp5 enhances sFgl2 secretion via ADAM17 and synergistically accelerates resolution of inflammation. These results uncover a previously unknown endogenous programmed mechanism by which Fgl2 regulates resolution of inflammation and shed new light on clinical sepsis treatments.

Topics: ADAM10 Protein; ADAM17 Protein; Adult; Animals; Docosahexaenoic Acids; Fibrinogen; Humans; Inflammation; Macrophages; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Middle Aged; Neutrophils; Sepsis; Young Adult

Myocardial infarction (MI) and subsequent progressive heart failure pathology is the major cause of death worldwide; however, the mechanism of this pathology remains unclear. The present work aimed at testing the hypothesis whether the inflammatory response is superimposed with the formation of bioactive lipid resolving molecules at the site of the injured myocardium in acute heart failure pathology post-MI. In this view, we used a robust permanent coronary ligation model to induce MI, leading to decreased contractility index with marked wall thinning and necrosis of the infarcted left ventricle. Then, we applied mass spectrometry imaging (MSI) in positive and negative ionization modes to characterize the spatial distribution of left ventricle lipids in the infarcted myocardium post-MI. After micro-extraction, liquid chromatography coupled to tandem mass spectrometry was used to confirm the structures of the imaged lipids. Statistical tools such as principal component analysis were used to establish a comprehensive visualization of lipid profile changes in MI and no-MI hearts. Resolving bioactive molecules such as resolvin (Rv) D1, RvD5, RvE3, 17-HDHA, LXA

Topics: Animals; Docosahexaenoic Acids; Heart; Inflammation; Lipid Metabolism; Lipids; Male; Mass Spectrometry; Mice, Inbred C57BL; Myocardial Infarction; Myocardium