scholarly journals Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1

2005 ◽  
Vol 201 (5) ◽  
pp. 713-722 ◽  
Author(s):  
Makoto Arita ◽  
Francesca Bianchini ◽  
Julio Aliberti ◽  
Alan Sher ◽  
Nan Chiang ◽  
...  
Keyword(s):  
Specific Binding ◽  
Nuclear Factor Κb ◽  
Receptor Activation ◽  
Lipid Mediator ◽  
Omega 3 ◽  
Complete Structure ◽  
Small Interference Rna ◽  
Stereochemical Assignment ◽  
Beneficial Effects ◽  
Human Disorders

The essential fatty acid eicosapentaenoic acid (EPA) present in fish oils displays beneficial effects in a range of human disorders associated with inflammation including cardiovascular disease. Resolvin E1 (RvE1), a new bioactive oxygenated product of EPA, was identified in human plasma and prepared by total organic synthesis. Results of bioaction and physical matching studies indicate that the complete structure of RvE1 is 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-EPA. At nanomolar levels, RvE1 dramatically reduced dermal inflammation, peritonitis, dendritic cell (DC) migration, and interleukin (IL) 12 production. We screened receptors and identified one, denoted earlier as ChemR23, that mediates RvE1 signal to attenuate nuclear factor–κB. Specific binding of RvE1 to this receptor was confirmed using synthetic [3H]-labeled RvE1. Treatment of DCs with small interference RNA specific for ChemR23 sharply reduced RvE1 regulation of IL-12. These results demonstrate novel counterregulatory responses in inflammation initiated via RvE1 receptor activation that provide the first evidence for EPA-derived potent endogenous agonists of antiinflammation.

Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3

2013 ◽  
Vol 153 (4) ◽  
pp. 355-360 ◽  
Author(s):  
Y. Isobe ◽  
M. Arita ◽  
R. Iwamoto ◽  
D. Urabe ◽  
H. Todoroki ◽  
...  
Keyword(s):  
Lipid Mediator ◽  
Omega 3 ◽  
Stereochemical Assignment ◽  
Anti Inflammatory

scholarly journals Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2868 ◽  
Author(s):  
Kento Sawane ◽  
Takahiro Nagatake ◽  
Koji Hosomi ◽  
So-ichiro Hirata ◽  
Jun Adachi ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Linseed Oil ◽  
Allergic Inflammation ◽  
Lipid Mediator ◽  
Nasal Passage ◽  
Peroxisome Proliferator ◽  
Omega 3 ◽  
Alpha Linolenic Acid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects

The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.

scholarly journals Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease Through the Resolvin E1 and ChemR23 Axis

Circulation ◽  
2020 ◽  
Vol 142 (8) ◽  
pp. 776-789 ◽  
Author(s):  
Gonzalo Artiach ◽  
Miguel Carracedo ◽  
Oscar Plunde ◽  
Craig E. Wheelock ◽  
Silke Thul ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Aortic Valve ◽  
Polyunsaturated Fatty Acids ◽  
Controlled Trial ◽  
Macrophage Polarization ◽  
Lipid Mediator ◽  
M2 Macrophage ◽  
Omega 3 ◽  
Aortic Valves ◽  
Beneficial Effects

Background: Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in cardiovascular prevention have recently been demonstrated in a large randomized, controlled trial. In addition, n-3 PUFAs serve as the substrate for the synthesis of specialized proresolving mediators, which are known by their potent beneficial anti-inflammatory, proresolving, and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and specialized proresolving mediators on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA–derived specialized proresolving mediators in relation to the development of AVS. Methods: Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe −/− mice and wire injury in C57BL/6J mice were used as models for mechanistic studies. Results: We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in noncalcified regions compared with calcified regions. Liquid chromatography tandem mass spectrometry–based lipid mediator lipidomics identified that the n-3 PUFA–derived specialized proresolving mediator resolvin E1 was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe −/− mice expressing the Caenorhabditis elegans Fat-1 transgene (Fat-1 tg ×Apoe −/− ), which enables the endogenous synthesis of n-3 PUFA and increased valvular n-3 PUFA content, exhibited reduced valve calcification, lower aortic valve leaflet area, increased M2 macrophage polarization, and improved echocardiographic parameters. Finally, abrogation of the resolvin E1 receptor ChemR23 enhanced disease progression, and the beneficial effects of Fat-1 tg were abolished in the absence of ChemR23. Conclusions: n-3 PUFA-derived resolvin E1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.

scholarly journals Simultaneous Pretreatment of Aspirin and Omega-3 Fatty Acid Attenuates Nuclear Factor-κB Activation in a Murine Model with Ventilator-Induced Lung Injury

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2258
Author(s):  
Won-Gun Kwack ◽  
Yoon-Je Lee ◽  
Eun-Young Eo ◽  
Jin-Haeng Chung ◽  
Jae-Ho Lee ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Fatty Acid ◽  
Lung Injury ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Omega 3 ◽  
Omega 3 Fatty Acid ◽  
Ventilator Induced Lung Injury ◽  
Sequential Administration ◽  
Pretreated Group

Ventilator-induced lung injury (VILI) is an important critical care complication. Nuclear factor-κB (NF-κB) activation, a critical signaling event in the inflammatory response, has been implicated in the tracking of the lung injury. The present study aimed to determine the effect of simultaneous pretreatment with enteral aspirin and omega-3 fatty acid on lung injury in a murine VILI model. We compared the lung inflammation after the sequential administration of lipopolysaccharides and mechanical ventilation between the pretreated simultaneous enteral aspirin and omega-3 fatty acid group and the non-pretreatment group, by quantifying NF-κB activation using an in vivo imaging system to detect bioluminescence signals. The pretreated group with enteral aspirin and omega-3 fatty acid exhibited a smaller elevation of bioluminescence signals than the non-pretreated group (p = 0.039). Compared to the non-pretreated group, the pretreatment group with simultaneous enteral aspirin and omega-3 fatty acid showed reduced expression of the pro-inflammatory cytokine, tumor necrosis factor-α, in bronchoalveolar lavage fluid (p = 0.038). Histopathological lung injury scores were also lower in the pretreatment groups compared to the only injury group. Simultaneous pretreatment with enteral administration of aspirin and omega-3 fatty acid could be a prevention method for VILI in patients with impending mechanical ventilation therapy.

scholarly journals Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 850
Author(s):  
María Ángeles Martín ◽  
Sonia Ramos
Keyword(s):  
Immune System ◽  
Fruits And Vegetables ◽  
Metabolic Diseases ◽  
Nuclear Factor Κb ◽  
Low Grade ◽  
Beneficial Effects ◽  
Health And Disease ◽  
Immunological Reactions ◽  
And Function ◽  
Positive Properties

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.

scholarly journals Heparin rescues factor V Leiden–associated placental failure independent of anticoagulation in a murine high-risk pregnancy model

Blood ◽  
2013 ◽  
Vol 121 (11) ◽  
pp. 2127-2134 ◽  
Author(s):  
Jianzhong An ◽  
Magarya S. Waitara ◽  
Michelle Bordas ◽  
Vidhyalakshmi Arumugam ◽  
Raymond G. Hoffmann ◽  
...  
Keyword(s):  
High Risk ◽  
Factor V Leiden ◽  
Receptor Activation ◽  
High Risk Pregnancy ◽  
Thrombin Receptor ◽  
Factor V ◽  
Beneficial Effects ◽  
Risk Pregnancy ◽  
Key Points ◽  
Placental Failure

Key Points Heparin may have beneficial effects on placental health beyond anticoagulation. Thrombin receptor activation on maternal platelets is implicated in placental developmental failure independent of thrombosis.

Abstract 1746: Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Mediates Vascular Repair By HDL Receptor Activation And Sphingosine Kinase (SK-1)/Sphingosine 1-Phosphate (S1P) Dependent Nitric Oxide (NO) Generation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Sergio Li Calzi ◽  
Jennifer L Kielczewski ◽  
Evan McFarland ◽  
Kyung Hee Chang ◽  
Aqeela Afzal ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Scavenger Receptor ◽  
Receptor Activation ◽  
Hematopoietic Stem ◽  
Beneficial Effects ◽  
Sphingosine 1 Phosphate ◽  
Active Motor ◽  
Umbilical Vein Endothelial Cells ◽  
Igfbp 3

Purpose: We demonstrated that IGFBP-3 stimulates hematopoietic stem cells (HSC) to differentiate into endothelial cells, form capillaries, and stabilize the vasculature (Chang, et al, PNAS 2007). Local IGFBP- 3 production is increased by hypoxia and facilitates the homing of HSC to areas of injury. In the circulation, IGFBP-3 is bound to HDL. In this study, we investigated the signaling pathways responsible for the robust migratory effects of IGFBP-3. Methods: The effects of IGFBP-3 on NO generation in human vascular precursors (CD 34 + , CD14 − ), human lung microvascular endothelial cells, and human umbilical vein endothelial cells were examined using DAF-FM fluorescence. Western analysis was use for detection of eNOS and vasodilator-stimulated phosphoprotein (VASP), which redistributes to lamellipodia forming an active motor complex that supports motility and is phosphorylated in response to NO. Localization of VASP was performed by immunohistochemistry. SK-1 was assessed following IGFBP-3 stimulation. Results: In CD34 + cells and endothelial cells, IGFBP-3 stimulated eNOS phosphorylation at Ser1177 (102 ± 1.8%, P = 0.0002) and increased NO generation (275 ± 50%, P = 0.05) by increasing SK-1 and S1P generation. IGFBP-3 was bound and internalized by the HDL receptor, scavenger receptor 1B (SR1B). NO generation following IGFBP-3 exposure was reduced by SK inhibitors or SR-1B blocking antibody pretreatment (35 ± 5%, P < 0.02). IGFBP-3 generated NO increased phosphorylation of VASP at Ser239 and promoted the redistribution of VASP to lamellipodia. Conclusions: IGFBP-3 effects on cell migration are NO dependent and mediated in part by activation of the HDL receptor SR1B suggesting that some of the beneficial effects of HDL are mediated by the association of IGFBP-3.

scholarly journals Chenodeoxycholic Acid from Bile Inhibits Influenza A Virus Replication via Blocking Nuclear Export of Viral Ribonucleoprotein Complexes

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3315 ◽  
Author(s):  
Ling Luo ◽  
Weili Han ◽  
Jinyan Du ◽  
Xia Yang ◽  
Mubing Duan ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Chenodeoxycholic Acid ◽  
Nuclear Export ◽  
Influenza A ◽  
Antiviral Agent ◽  
Dietary Fats ◽  
Lipid Mediator ◽  
Omega 3 ◽  
Ribonucleoprotein Complexes

Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC50 ranging from 5.5 to 11.5 μM. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections.

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