5,147 results match your criteria Prostaglandins Leukotrienes & Essential Fatty Acids [Journal]


Effects of anti-inflammatory and adaptogenic herbal extracts on gene expression of eicosanoids signaling pathways in isolated brain cells.

Phytomedicine 2019 Mar 10:152881. Epub 2019 Mar 10.

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address:

Introduction: The adaptogens modulate expression of genes playing key roles in development of aging-related disorders, which are considered as low-grade systemic inflammatory conditions characterized by an imbalance between pro-and anti-inflammatory eicosanoids.

Aim Of The Study: We compared the effects of anti-inflammatory and adaptogenic plant extracts on the expression of genes involved in biosynthesis of eicosanoids with the purpose to find those plants, which selectively upregulated the expression of anti-inflammatory lipoxins signaling pathways and inhibited pro-inflammatory signaling pathways associated with biosynthesis of leukotrienes, prostaglandins and thromboxanes.

Materials And Methods: We conducted transcriptome-wide RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of plant extract and analyzed the relevance of deregulated genes to eicosanoids signaling pathways using in silico models. Read More

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http://dx.doi.org/10.1016/j.phymed.2019.152881DOI Listing

AK106-001616, a potent and selective inhibitor of cytosolic phospholipase A2: in vivo efficacy for inflammation, neuropathic pain, and pulmonary fibrosis.

J Pharmacol Exp Ther 2019 Apr 10. Epub 2019 Apr 10.

Asahi Kasei Pharma Co. Ltd.

AK106-001616 is a novel, potent, and selective inhibitor of the cytosolic phospholipase A2 (cPLA2) enzyme. Unlike traditional non-steroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors, AK106-001616 reduced prostaglandin (PG) E2 and leukotriene (LT) B4 production by stimulated cells. The suppression of PGE2 and LTB4 production was also confirmed using an air pouch model in rats administered a single oral dose of AK106-001616. Read More

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http://dx.doi.org/10.1124/jpet.118.255034DOI Listing
April 2019
2 Reads

Dynamic changes to lipid mediators support transitions among macrophage subtypes during muscle regeneration.

Nat Immunol 2019 05 1;20(5):626-636. Epub 2019 Apr 1.

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Muscle damage elicits a sterile immune response that facilitates complete regeneration. Here, we used mass spectrometry-based lipidomics to map the mediator lipidome during the transition from inflammation to resolution and regeneration in skeletal muscle injury. We observed temporal regulation of glycerophospholipids and production of pro-inflammatory lipid mediators (for example, leukotrienes and prostaglandins) and specialized pro-resolving lipid mediators (for example, resolvins and lipoxins) that were modulated by ibuprofen. Read More

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http://dx.doi.org/10.1038/s41590-019-0356-7DOI Listing
May 2019
20.004 Impact Factor

Beyond leukotriene formation-The noncanonical functions of 5-lipoxygenase.

Prostaglandins Other Lipid Mediat 2019 Mar 28;142:24-32. Epub 2019 Mar 28.

Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, 60438 Frankfurt, Germany. Electronic address:

5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of leukotrienes and specialized proresolving lipid mediators (SPM). It is mainly expressed in leukocytes and is part of the innate immune system. 5-LO can shuttle between the cytosol and the nucleus. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10988823193001
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http://dx.doi.org/10.1016/j.prostaglandins.2019.03.003DOI Listing
March 2019
3 Reads

Cellular and molecular mechanisms of the preovulatory follicle differenciation and ovulation: What do we know in the mare relative to other species.

Theriogenology 2019 May 19;130:163-176. Epub 2019 Mar 19.

PRC, INRA, CNRS, IFCE, Université de Tours, 37380, Nouzilly, France.

Terminal follicular differentiation and ovulation are essential steps of reproduction. They are induced by the increase in circulating LH, and lead to the expulsion from the ovary of oocytes ready to be fertilized. This review summarizes our current understanding of cellular and molecular pathways that control ovulation using a broad mammalian literature, with a specific focus to the mare, which is unique in some aspects of ovarian function in some cases. Read More

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http://dx.doi.org/10.1016/j.theriogenology.2019.03.007DOI Listing
May 2019
4 Reads

Pro-resolving lipid mediators as therapeutic leads for cardiovascular diseases.

Expert Opin Ther Targets 2019 Mar 27:1-14. Epub 2019 Mar 27.

b School of Chinese Medicine , The University of Hong Kong , Hong Kong , China.

Introduction: Cardiovascular diseases are the leading cause of human death globally. Lipid mediators contribute to the initiation and resolution of inflammation in the pathogenesis of cardiovascular diseases. These resolving lipid mediators antagonize the effects of pro-inflammatory prostaglandins (PGs) and leukotrienes (LTs) on macrophage/neutrophil infiltration, enhance macrophage phagocytosis towards apoptotic cells, and accelerate tissue repair. Read More

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http://dx.doi.org/10.1080/14728222.2019.1599360DOI Listing

Quantitative metabolic profiling of urinary eicosanoids for clinical phenotyping.

J Lipid Res 2019 Mar 6. Epub 2019 Mar 6.

Karolinska Institute, Sweden;

The eicosanoids are a family of lipid mediators of pain and inflammation involved in multiple pathologies, including asthma, hypertension, cancer, atherosclerosis, and neurodegenerative diseases. These signaling mediators act locally, but are rapidly metabolized and transported to the systemic circulation as a mixture of primary and secondary metabolites. Accordingly, urine has become a useful readily accessible biofluid for monitoring the endogenous synthesis of these metabolites. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.D090571
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http://dx.doi.org/10.1194/jlr.D090571DOI Listing
March 2019
19 Reads
4.421 Impact Factor

Novel benzoxanthene lignans that favorably modulate lipid mediator biosynthesis: A promising pharmacological strategy for anti-inflammatory therapy.

Biochem Pharmacol 2019 Mar 2. Epub 2019 Mar 2.

Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, D-7743 Jena, Germany. Electronic address:

Lipid mediators (LM) encompass pro-inflammatory prostaglandins (PG) and leukotrienes (LT) but also specialized pro-resolving mediators (SPM) which display pivotal bioactivities in health and disease. Pharmacological intervention with inflammatory disorders such as osteoarthritis and rheumatoid arthritis commonly employs anti-inflammatory drugs that can suppress PG and LT formation, which however, possess limited effectiveness and side effects. Here, we report on the discovery and characterization of the two novel benzoxanthene lignans 1 and 2 that modulate select LM biosynthetic enzymes enabling the switch from pro-inflammatory LT to SPM biosynthesis as potential pharmacological strategy to intervene with inflammation. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.03.003DOI Listing
March 2019
1 Read

Leukotriene B modulation of murine dendritic cells affects adaptive immunity.

Prostaglandins Other Lipid Mediat 2019 04 8;141:34-39. Epub 2019 Feb 8.

Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address:

Dendritic cells (DCs) link innate and adaptive immunity. The microenvironment generated during the innate immunity affects DCs and the type of adaptive immunity generated. Lipid mediators are released early in inflammation and could modify the functional state of DCs. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10988823183011
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http://dx.doi.org/10.1016/j.prostaglandins.2019.02.001DOI Listing
April 2019
6 Reads

Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome.

FASEB J 2019 Feb 8:fj201802509R. Epub 2019 Feb 8.

Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany.

Nonsteroidal anti-inflammatory drugs interfere with the metabolism of arachidonic acid to proinflammatory prostaglandins and leukotrienes by targeting cyclooxygenases (COXs), 5-lipoxygenase (LOX), or the 5-LOX-activating protein (FLAP). These and related enzymes act in conjunction with marked crosstalk within a complex lipid mediator (LM) network where also specialized proresolving LMs (SPMs) are formed. Here, we present how prominent LM pathways can be differentially modulated in human proinflammatory M1 and proresolving M2 macrophage phenotypes that, upon exposure to Escherichia coli, produce either abundant prostaglandins and leukotrienes (M1) or SPMs (M2). Read More

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http://dx.doi.org/10.1096/fj.201802509RDOI Listing
February 2019

LC/MS/MS analyses of open-flow microperfusion samples quantify eicosanoids in a rat model of skin inflammation.

J Lipid Res 2019 Apr 29;60(4):758-766. Epub 2019 Jan 29.

Joanneum Research Forschungsgesellschaft mbH, Institute for Biomedicine and Health Sciences, Graz, Austria

Eicosanoids are lipid-mediator molecules with key roles in inflammatory skin diseases, such as psoriasis. Eicosanoids are released close to the source of inflammation, where they elicit local pleiotropic effects and dysregulations. Monitoring inflammatory mediators directly in skin lesions could provide new insights and therapeutic possibilities. Read More

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http://www.jlr.org/lookup/doi/10.1194/jlr.M087221
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http://dx.doi.org/10.1194/jlr.M087221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446707PMC
April 2019
10 Reads

Eicosanoids in tissue repair.

Immunol Cell Biol 2019 Mar 24;97(3):279-288. Epub 2019 Jan 24.

Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, 80802, Munich, Germany.

Trauma or infection can result in tissue damage, which needs to be repaired in a well-orchestrated manner to restore tissue function and homeostasis. Lipid mediators derived from arachidonic acid (termed eicosanoids) play central and versatile roles in the regulation of tissue repair. Here, I summarize the current state-of the-art regarding the functional activities of eicosanoids in tissue repair responses during homeostasis and disease. Read More

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http://dx.doi.org/10.1111/imcb.12226DOI Listing
March 2019
1 Read

Characterization of cysteinyl leukotriene-related receptors and their interactions in a mouse model of asthma.

Prostaglandins Leukot Essent Fatty Acids 2019 Feb 12;141:17-23. Epub 2018 Dec 12.

Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. Electronic address:

Identification of the characterization of cysteinyl leukotrienes receptor (CysLTRs) could facilitate our understanding of these receptors' role in asthma. We aimed to investigate the localization and interactions of CysLTRs using a mouse model of asthma. BALB/c mice were administered ovalbumin (OVA) to induce allergic asthma. Read More

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http://dx.doi.org/10.1016/j.plefa.2018.12.002DOI Listing
February 2019
4 Reads

Transcriptomic and lipidomic profiling of eicosanoid/docosanoid signalling in affected and non-affected skin of human atopic dermatitis patients.

Exp Dermatol 2019 Feb;28(2):177-189

Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.

Lipoxygenases (LOX) and cyclooxygenase (COX) are the main enzymes for PUFA metabolism to highly bio-active prostaglandins, leukotrienes, thromboxanes, lipoxins, resolvins and protectins. LOX and COX pathways are important for the regulation of pro-inflammatory or pro-resolving metabolite synthesis and metabolism for various inflammatory diseases such as atopic dermatitis (AD). In this study, we determined PUFAs and PUFA metabolites in serum as well as affected and non-affected skin samples from AD patients and the dermal expression of various enzymes, binding proteins and receptors involved in these LOX and COX pathways. Read More

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http://dx.doi.org/10.1111/exd.13867DOI Listing
February 2019
6 Reads

Novel mediators and mechanisms in the resolution of infectious inflammation: evidence for vagus regulation.

J Intern Med 2018 Dec 19. Epub 2018 Dec 19.

Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Excessive chronic inflammation is linked to many diseases and considered a stress factor in humans (Robbins Pathologic Basis of Disease. Philadelphia: W.B. Read More

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http://dx.doi.org/10.1111/joim.12871DOI Listing
December 2018
3 Reads

Pathogenesis of NSAID-induced reactions in aspirin-exacerbated respiratory disease.

Authors:
Tanya M Laidlaw

World J Otorhinolaryngol Head Neck Surg 2018 Sep 5;4(3):162-168. Epub 2018 Sep 5.

Brigham and Women's Hospital, Division of Rheumatology, Immunology and Allergy, Boston, MA, USA.

It is well-established that following ingestion of aspirin or any other inhibitor of cyclooxygenase-1, patients with Samter's disease, or aspirin-exacerbated respiratory disease (AERD) develop the sudden onset of worsening respiratory clinical symptoms, which usually involves nasal congestion, rhinorrhea, wheezing and bronchospasm. Gastrointestinal distress, nausea, a pruritic rash and angioedema can also occasionally develop. However, the underlying pathologic mechanism that drives these clinical reactions remains elusive. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S20958811183012
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http://dx.doi.org/10.1016/j.wjorl.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251957PMC
September 2018
22 Reads

The COX-2/prostanoid signaling cascades in seizure disorders.

Expert Opin Ther Targets 2019 Jan 2;23(1):1-13. Epub 2018 Dec 2.

a Department of Pharmacology , Emory University School of Medicine , Atlanta , GA , USA.

Introduction:A robust neuroinflammatory response is a prevalent feature of multiple neurological disorders, including epilepsy and acute status epilepticus. One component of this neuroinflammatory reaction is the induction of cyclooxygenase-2 (COX-2), synthesis of several prostaglandins and endocannabinoid metabolites, and subsequent activation of prostaglandin and related receptors. Neuroinflammation mediated by COX-2 and its downstream effectors has received considerable attention as a potential target class to ameliorate the deleterious consequences of neurological injury. Read More

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https://www.tandfonline.com/doi/full/10.1080/14728222.2019.1
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http://dx.doi.org/10.1080/14728222.2019.1554056DOI Listing
January 2019
14 Reads

Determination of potential childhood asthma biomarkers using a powerful methodology based on microextraction by packed sorbent combined with ultra-high pressure liquid chromatography. Eicosanoids as case study.

J Chromatogr A 2019 Jan 22;1584:42-56. Epub 2018 Nov 22.

CQM - Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal; Faculdade de Ciências Exatas e da Engenharia, Universidade da Madeira, Campus Universitário da Penteada, 9020-105, Funchal, Portugal. Electronic address:

Leukotrienes and prostaglandins are arachidonic acid bioactive derived eicosanoids and key mediators of bronchial inflammation and response modulation in the airways contributing to the pathophysiology of asthma. An easy-to-use ultra-high pressure liquid chromatography (UHPLC)-based strategy was developed to characterize biomarkers of lipid peroxidation: leukotrienes E (LTE) and B (LTB) and 11β-prostaglandin F (11βPGF), present in urine of asthmatic patients (N = 27) and healthy individuals (N = 17). A semi-automatic eVol®-microextraction by packed sorbent (MEPS) was used to isolate the target analytes. Read More

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http://dx.doi.org/10.1016/j.chroma.2018.11.041DOI Listing
January 2019
1 Read

The Immunomodulatory and Anti-Inflammatory Role of Polyphenols.

Nutrients 2018 Nov 2;10(11). Epub 2018 Nov 2.

Cellular and Molecular Medicine Department, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H8L1, Canada.

This review offers a systematic understanding about how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms. It provides a clear understanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate immunity by interfering with immune cell regulation, proinflammatory cytokines' synthesis, and gene expression. Read More

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http://www.mdpi.com/2072-6643/10/11/1618
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http://dx.doi.org/10.3390/nu10111618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266803PMC
November 2018
30 Reads

5-lipoxygenase-dependent biosynthesis of novel 20:4 n-3 metabolites with anti-inflammatory activity.

Prostaglandins Leukot Essent Fatty Acids 2018 Nov 16;138:38-44. Epub 2018 Oct 16.

Départment de Chimie et Biochimie, Université de Moncton, 18 Antonine-Maillet Avenue, Moncton, NB E1A 3E9, Canada. Electronic address:

5-lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) into pro-inflammatory leukotrienes. N-3 PUFA like eicosapentaenoic acid are subject to a similar metabolism and are precursors of pro-resolving mediators. Stearidonic acid (18:4 n-3, SDA) is a plant source of n-3 PUFA that is elongated to 20:4 n-3, an analogue of AA. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09523278183018
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http://dx.doi.org/10.1016/j.plefa.2018.10.005DOI Listing
November 2018
4 Reads

Targeting cysteinyl-leukotrienes in abdominal aortic aneurysm.

Prostaglandins Other Lipid Mediat 2018 11 21;139:24-28. Epub 2018 Sep 21.

Division of Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 65 Solna, Sweden. Electronic address:

Abdominal aortic aneurysm (AAA) is an asymptomatic dilatation of the vessel wall exceeding the normal vessel diameter by 50%, accompanied by intramural thrombus formation. Since the aneurysm can rupture, AAA is a life-threatening vascular disease, which may be amenable to surgical repair. At present, no pharmacological therapy for AAA is available. Read More

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http://dx.doi.org/10.1016/j.prostaglandins.2018.09.007DOI Listing
November 2018
2 Reads
2.380 Impact Factor

Eicosanoid Control Over Antigen Presenting Cells in Asthma.

Front Immunol 2018 4;9:2006. Epub 2018 Sep 4.

Laboratory of Immunoregulation, VIB-UGent Center for Inflammation Research, Ghent, Belgium.

Asthma is a common lung disease affecting 300 million people worldwide. Allergic asthma is recognized as a prototypical Th2 disorder, orchestrated by an aberrant adaptive CD4+ T helper (Th2/Th17) cell immune response against airborne allergens, that leads to eosinophilic inflammation, reversible bronchoconstriction, and mucus overproduction. Other forms of asthma are controlled by an eosinophil-rich innate ILC2 response driven by epithelial damage, whereas in some patients with more neutrophilia, the disease is driven by Th17 cells. Read More

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http://dx.doi.org/10.3389/fimmu.2018.02006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131302PMC
September 2018
2 Reads

Role of Histamine in Modulating the Immune Response and Inflammation.

Mediators Inflamm 2018 27;2018:9524075. Epub 2018 Aug 27.

Laboratory of Dermatology and Immunodeficiencies, LIM-56, Tropical Medical Institute, Department of Dermatology, School of Medicine, University of São Paulo, Sao Paulo, SP, Brazil.

Inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, and leukotrienes, impact the immune system, usually as proinflammatory factors. Other mediators act as regulatory components to establish homeostasis after injury or prevent the inflammatory process. Histamine, a biogenic vasoactive amine, causes symptoms such as allergies and has a pleiotropic effect that is dependent on its interaction with its four histamine receptors. Read More

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https://www.hindawi.com/journals/mi/2018/9524075/
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http://dx.doi.org/10.1155/2018/9524075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129797PMC
January 2019
14 Reads

Cyclooxygenase pathway mediates the inhibition of Na-glutamine co-transporter B0AT1 in rabbit villus cells during chronic intestinal inflammation.

PLoS One 2018 7;13(9):e0203552. Epub 2018 Sep 7.

Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Medical Center Drive, Huntington, WV, United States of America.

In the mammalian intestine, glutamine assimilation by the absorptive villus cells is mediated by Na-glutamine co-transport, specifically by B0AT1. In a rabbit model of chronic intestinal inflammation, B0AT1 is inhibited secondary to a decrease in the number of co-transporters in the brush border membrane (BBM). This inhibition can be reversed by treatment with a broad-spectrum immune modulator such as glucocorticoid suggesting that immune inflammatory mediators may regulate B0AT1 during chronic intestinal inflammation. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203552PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128596PMC
February 2019
1 Read

Inflammatory and Pro-resolving Lipids in Trypanosomatid Infections: A Key to Understanding Parasite Control.

Front Microbiol 2018 21;9:1961. Epub 2018 Aug 21.

Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Pathogenic trypanosomatids (, and spp.) are protozoan parasites that cause neglected diseases affecting millions of people in Africa, Asia, and the Americas. In the process of infection, trypanosomatids evade and survive the immune system attack, which can lead to a chronic inflammatory state that induces cumulative damage, often killing the host in the long term. Read More

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http://dx.doi.org/10.3389/fmicb.2018.01961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113562PMC
August 2018
2 Reads

Metabolites of prostaglandin synthases as potential biomarkers of Lyme disease severity and symptom resolution.

Inflamm Res 2019 Jan 18;68(1):7-17. Epub 2018 Aug 18.

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College Street, Toronto, ON, M5S3E2, Canada.

Background: Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia burgdorferi. The role of the inflammatory processes mediated by prostaglandins (PGs), thromboxanes and leukotrienes (LTs) in LB severity and symptoms resolution is yet to be elucidated. Read More

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http://dx.doi.org/10.1007/s00011-018-1180-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314976PMC
January 2019
15 Reads

Simultaneous determination of PUFA-derived pro-resolving metabolites and pathway markers using chiral chromatography and tandem mass spectrometry.

Anal Chim Acta 2018 Nov 8;1031:185-194. Epub 2018 May 8.

pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Frankfurt, Germany. Electronic address:

Lipid mediators play an important role as biological messengers involved in inflammatory processes. Deriving from different polyunsaturated fatty acids, endogenously built mediators featuring both pro- and anti-inflammatory properties as well as pro-resolving lipid mediators and their biological precursors have been investigated. A newly developed method using chiral chromatography-tandem mass spectrometry on human plasma has demonstrated its suitability for the simultaneous determination of prostaglandins, lipoxins, D-series derived resolvins as well as protectins, maresin 1, leukotriene B4 and several precursors of them in order to yield information about metabolic pathways. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00032670183060
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http://dx.doi.org/10.1016/j.aca.2018.05.020DOI Listing
November 2018
13 Reads

Bioactive lipid metabolism in platelet "first responder" and cancer biology.

Cancer Metastasis Rev 2018 09;37(2-3):439-454

Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.

Platelets can serve as "first responders" in cancer and metastasis. This is partly due to bioactive lipid metabolism that drives both platelet and cancer biology. The two primary eicosanoid metabolites that maintain platelet rapid response homeostasis are prostacyclin made by endothelial cells that inhibits platelet function, which is counterbalanced by thromboxane produced by platelets during activation, aggregation, and platelet recruitment. Read More

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http://dx.doi.org/10.1007/s10555-018-9755-8DOI Listing
September 2018
5 Reads

Using quantitative systems pharmacology to evaluate the drug efficacy of COX-2 and 5-LOX inhibitors in therapeutic situations.

NPJ Syst Biol Appl 2018 3;4:28. Epub 2018 Aug 3.

1Institute of Applied Microbiology (iAMB), Aachen Biology and Biotechnology (ABBt), RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany.

A quantitative analysis of dose-response relationships is essential in preclinical and clinical drug development in order to optimize drug efficacy and safety, respectively. However, there is a lack of quantitative understanding about the dynamics of pharmacological drug-target interactions in biological systems. In this study, a quantitative systems pharmacology (QSP) approach is applied to quantify the drug efficacy of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors by coupling physiologically based pharmacokinetic models, at the whole-body level, with affected biological networks, at the cellular scale. Read More

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http://dx.doi.org/10.1038/s41540-018-0062-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072773PMC
August 2018
4 Reads

Lipid Mediator Quantification in Isolated Human and Guinea Pig Airways: An Expanded Approach for Respiratory Research.

Anal Chem 2018 09 20;90(17):10239-10248. Epub 2018 Aug 20.

Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics , Karolinska Institutet , 17177 Stockholm , Sweden.

The clinical importance of prostaglandins and leukotrienes in asthma is well recognized; however, the biochemical role of other lipid mediators (often termed oxylipins) in the regulation of airway tone and inflammation remains unclear. We therefore developed a workflow to investigate oxylipin physiology and pharmacology in two in vitro models, the intact human bronchus and the guinea pig trachea. Airways were isolated and smooth muscle contraction was measured in an organ bath following stimulation with either anti-IgE or ovalbumin. Read More

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http://dx.doi.org/10.1021/acs.analchem.8b01651DOI Listing
September 2018
7 Reads

Mast Cell Mediators of Significance in Clinical Practice in Mastocytosis.

Immunol Allergy Clin North Am 2018 08 9;38(3):397-410. Epub 2018 Jun 9.

Division of Allergic Diseases, Mayo Clinic, 200 Southwest 1st Street, Rochester, MN 55902, USA.

Mast cells leave evidence, a "fingerprint," of their participation in acute and chronic clinical events. That fingerprint is an elevation, either chronic or acute, in levels of their secreted mediators or their metabolites. Of these, only serum tryptase is currently one of the diagnostic criteria for systemic mastocytosis or mast cell activation. Read More

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http://dx.doi.org/10.1016/j.iac.2018.04.011DOI Listing
August 2018
16 Reads

Eicosanoids and HB-EGF/EGFR in cancer.

Cancer Metastasis Rev 2018 09;37(2-3):385-395

Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan.

Eicosanoids are bioactive lipids that play crucial roles in various pathophysiological conditions, including inflammation and cancer. They include both the COX-derived prostaglandins and the LOX-derived leukotrienes. Furthermore, the epidermal growth factor receptor (EGFR) pathways family of receptor tyrosine kinases also are known to play a central role in the tumorigenesis. Read More

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http://dx.doi.org/10.1007/s10555-018-9746-9DOI Listing
September 2018
1 Read

Bioanalytical insights into the association between eicosanoids and pathogenesis of hepatocellular carcinoma.

Cancer Metastasis Rev 2018 09;37(2-3):269-277

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, National Engineering Research Center for Functional Food, National Engineering Laboratory for Cereal Fermentation Technology, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, People's Republic of China.

It has been noted that inflammatory were intimately associated with the development and progression of hepatocellular carcinoma (HCC). Eicosanoids derived from arachidonic acid play crucial roles in chronic inflammation. Accordingly, there is an intricate relationship between eicosanoids and HCC, being supported by the epidemiological, clinical, and basic science studies. Read More

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http://link.springer.com/10.1007/s10555-018-9747-8
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http://dx.doi.org/10.1007/s10555-018-9747-8DOI Listing
September 2018
4 Reads

miR-146a suppresses 5-lipoxygenase activating protein (FLAP) expression and Leukotriene B4 production in lung cancer cells.

Oncotarget 2018 Jun 1;9(42):26751-26769. Epub 2018 Jun 1.

Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers Biomedical and Health Sciences, New Jersey Medical School and the School of Graduate Studies, Health Sciences Campus, Newark, NJ, USA.

Arachidonic acid (AA) can be converted into prostaglandins (PGs) or leukotrienes (LTs) by the enzymatic actions of cyclooxygenases (COX-1 and COX-2) or 5-lipoxygenase (5-LO), respectively. PGs and LTs are lipid signaling molecules that have been implicated in various diseases, including multiple cancers. 5-LO and its activating protein (FLAP) work together in the first two conversion steps of LT production. Read More

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http://www.oncotarget.com/fulltext/25482
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http://dx.doi.org/10.18632/oncotarget.25482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003571PMC
June 2018
2 Reads

LTB and PGE modulate the release of MIP-1α and IL-1β by cells stimulated with Bothrops snake venoms.

Toxicon 2018 Aug 9;150:289-296. Epub 2018 Jun 9.

Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo (FCFRP-USP), Avenida do Café, s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil. Electronic address:

Envenomation by Bothrops snakes promotes the release of inflammatory mediators, whose effects during this context are not well understood. These mediators include chemokines, cytokines and eicosanoids. Indeed, Bothrops snake envenomation results in local and systemic perturbations, including leukocyte recruitment, edema, pain and extensive tissue damage. Read More

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http://dx.doi.org/10.1016/j.toxicon.2018.06.066DOI Listing
August 2018
4 Reads

Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: A structure-based approach.

Eur J Pharm Sci 2018 08 5;121:356-381. Epub 2018 Jun 5.

Department of Pharmaceutical Chemistry, St. James College of Pharmaceutical Sciences, Chalakudy, Kerala, India.

Inflammatory mediators of the arachidonic acid cascade from cyclooxygenase (COX) and lipoxygenase (LOX) pathways are primarily responsible for many diseases in human beings. Chronic inflammation is associated with the pathogenesis and progression of cancer, arthritis, autoimmune, cardiovascular and neurological diseases. Traditional non-steroidal anti-inflammatory agents (tNSAIDs) inhibit cyclooxygenase pathway non-selectively and produce gastric mucosal damage due to COX-1 inhibition and allergic reactions and bronchospasm resulting from increased leukotriene levels. Read More

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http://dx.doi.org/10.1016/j.ejps.2018.06.003DOI Listing
August 2018
2 Reads

Prominent release of lipoxygenase generated mediators in a murine house dust mite-induced asthma model.

Prostaglandins Other Lipid Mediat 2018 07 12;137:20-29. Epub 2018 May 12.

Unit for Experimental Asthma and Allergy Research, The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address:

The profile of activation of lipid mediator (LM) pathways in asthmatic airway inflammation remains unclear. This experimental study quantified metabolite levels of ω3-, ω6- and ω9-derived polyunsaturated fatty acids in bronchoalveolar lavage fluid (BALF) after 4-weeks of repeated house dust mite (HDM) exposure in a murine (C57BL/6) asthma model. The challenge induced airway hyperresponsiveness, pulmonary eosinophil infiltration, but with low and unchanged mast cell numbers. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10988823183002
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http://dx.doi.org/10.1016/j.prostaglandins.2018.05.005DOI Listing
July 2018
4 Reads

Lipid mediator Leukotriene D-induces airway epithelial cells proliferation through EGFR/ERK1/2 pathway.

Prostaglandins Other Lipid Mediat 2018 05 8;136:55-63. Epub 2018 May 8.

School of Life Sciences, Central University of Gujarat, Gandhinagar, 382030, Gujarat, India. Electronic address:

Background: Cysteinyl leukotrienes (CysLTs), the potent lipid inflammatory mediators, are elevated in many pathological conditions and implicated in various inflammatory diseases including asthma, however their role in airway epithelial cells modulation is not clearly understood. We have investigated the effects of a CysLT, Leukotriene D (LTD) on human airway epithelial cells, and assessed its role and mode of action in these cells.

Methodology: Human small airway epithelial cells (SAECs) and A549 cells were incubated with different concentrations of LTD for different time intervals. Read More

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http://dx.doi.org/10.1016/j.prostaglandins.2018.05.003DOI Listing
May 2018
1 Read

Communicating with the dead: lipids, lipid mediators and extracellular vesicles.

Biochem Soc Trans 2018 06 9;46(3):631-639. Epub 2018 May 9.

School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.

Apoptosis is a key event in the control of inflammation. However, for this to be successful, dying cells must efficiently and effectively communicate their presence to phagocytes to ensure timely removal of dying cells. Here, we consider apoptotic cell-derived extracellular vesicles and the role of contained lipids and lipid mediators in ensuring effective control of inflammation. Read More

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http://biochemsoctrans.org/lookup/doi/10.1042/BST20160477
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http://dx.doi.org/10.1042/BST20160477DOI Listing
June 2018
6 Reads

SIRT1 attenuates murine allergic rhinitis by downregulated HMGB 1/TLR4 pathway.

Scand J Immunol 2018 Jun;87(6):e12667

International Clinic, Qingdao Municipal Hospital (Eastern Campus), Qingdao, China.

Conventional allergic rhinitis (AR) treatments have limitations due to the lack of safety and complete cure strategy. We evaluated the effects of silent information regulator 1 (SIRT1), a multifunctional molecule involved in a variety of inflammatory pathways, on murine AR model. Ovalbumin (OVA)-induced murine model was constructed, and recombinant SIRT1 was administered into the nostril continuously. Read More

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http://dx.doi.org/10.1111/sji.12667DOI Listing
June 2018
4 Reads

Extracellular Vesicles as Conveyors of Membrane-Derived Bioactive Lipids in Immune System.

Int J Mol Sci 2018 Apr 18;19(4). Epub 2018 Apr 18.

Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, Italy.

Over the last 20 years, extracellular vesicles (EVs) have been established as an additional way to transmit signals outside the cell. They are membrane-surrounded structures of nanometric size that can either originate from the membrane invagination of multivesicular bodies of the late endosomal compartment (exosomes) or bud from the plasma membrane (microvesicles). They contain proteins, lipids, and nucleic acids—namely miRNA, but also mRNA and lncRNA—which are derived from the parental cell, and have been retrieved in every fluid of the body. Read More

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http://dx.doi.org/10.3390/ijms19041227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979532PMC
April 2018
8 Reads

Increased expression of CysLT receptors in the lung of asthmatic mice and role in allergic responses.

Prostaglandins Leukot Essent Fatty Acids 2018 04 22;131:24-31. Epub 2018 Mar 22.

Department of Immunopharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan. Electronic address:

Compared with CysLT receptors, the functional role of CysLT receptors in asthma has not been clarified. The purpose of this study was to determine 1) whether CysLT receptors are expressed in the lung of mice and if expression increases in asthmatic mice, and 2) whether CysLT receptors are involved in allergic leukocyte infiltration into the lung and in the development of airway remodeling in asthmatic mice. BALB/c mice were sensitized with ovalbumin (OVA) + Al(OH), and intratracheally challenged with OVA 4 times. Read More

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http://dx.doi.org/10.1016/j.plefa.2018.03.007DOI Listing
April 2018
3 Reads

Omega-6 fatty acids and inflammation.

Prostaglandins Leukot Essent Fatty Acids 2018 05 22;132:41-48. Epub 2018 Mar 22.

Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, IDS Building, MP887 Southampton General Hospital, Tremona Road, Southampton SO16 6YD, United Kingdom; National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO16 6YD, United Kingdom. Electronic address:

Inflammation is a normal process that is part of host defence and tissue healing. However, excessive or unresolved inflammation can lead to uncontrolled tissue damage, pathology and disease. In humans on a Western diet, the omega-6 polyunsaturated fatty acid arachidonic acid (ARA) makes a significant contribution to the fatty acids present in the membrane phospholipids of cells involved in inflammation. Read More

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http://dx.doi.org/10.1016/j.plefa.2018.03.004DOI Listing
May 2018
2 Reads

Mast cell disorders: Protean manifestations and treatment responses.

Ann Allergy Asthma Immunol 2018 07 28;121(1):128-130. Epub 2018 Mar 28.

Department of Medicine, University of California San Diego, San Diego, California. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2018.03.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026564PMC
July 2018
2 Reads

Identification of multi-target inhibitors of leukotriene and prostaglandin E biosynthesis by structural tuning of the FLAP inhibitor BRP-7.

Eur J Med Chem 2018 Apr 17;150:876-899. Epub 2018 Mar 17.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Yenimahalle, 06330, Ankara, Turkey. Electronic address:

Leukotrienes (LTs) and prostaglandin (PG)E are enzymatically produced from arachidonic acid and represent highly bioactive lipid mediators with pro-inflammatory functions. Here, we report on novel multi-target inhibitors that potently and dually interfere with 5-lipoxygenase-activating protein (FLAP) and microsomal prostaglandin E synthase (mPGES)-1 in LT and PGE biosynthesis, based on the previously identified selective FLAP inhibitor BRP-7 (8, IC = 0.31 μM). Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.03.045DOI Listing
April 2018
13 Reads

The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

Prostaglandins Other Lipid Mediat 2018 05 22;136:1-8. Epub 2018 Mar 22.

Medical School, University of Western Australia, Australia.

Background: Neutrophils release leukotriene (LT)B and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB. Read More

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http://dx.doi.org/10.1016/j.prostaglandins.2018.03.002DOI Listing
May 2018
3 Reads

Metabololipidomic profiling of functional immunoresolvent clusters and eicosanoids in mammalian tissues.

Biochem Biophys Res Commun 2018 10 15;504(3):553-561. Epub 2018 Mar 15.

Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, 60 Fenwood Road, BTM 3016, Boston, MA, 02115, USA. Electronic address:

Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels. Read More

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http://dx.doi.org/10.1016/j.bbrc.2018.03.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139088PMC
October 2018
12 Reads

Nonsteroidal anti-inflammatory drug hypersensitivity: not always an allergy!

Neth J Med 2018 Mar;76(2):52-59

Department of Internal Medicine, section Allergy and Clinical Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of hypersensitivity reactions. Several distinct clinical syndromes are described regarding NSAID hypersensitivity. Such a reaction is generally caused by a non-immunological mechanism. Read More

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March 2018
4 Reads

The influence of arachidonic acid metabolites on PPAR and RXR expression in bovine uterine cells.

Gen Comp Endocrinol 2018 06 3;262:27-35. Epub 2018 Mar 3.

Department of Biodiversity Protection, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Olsztyn, Tuwima St. 10, 10-747 Olsztyn, Poland. Electronic address: http://tbr.pan.olsztyn.pl/images/KSIAZKA_KONFERENCYJNA_TBR_30_08_17.pdf.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the superfamily of nuclear receptors. Three isoforms have been described: alpha (PPARα), delta (PPARδ), and gamma (PPARγ). PPARs heterodimerize with retinoid X receptors (RXRs: RXRα, RXRβ and RXRγ). Read More

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http://dx.doi.org/10.1016/j.ygcen.2018.03.009DOI Listing
June 2018
2 Reads