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Leukotrienes

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https://www.readbyqxmd.com/read/28098359/m2-like-macrophages-induce-colon-cancer-cell-invasion-via-matrix-metalloproteinases
#1
Katyayni Vinnakota, Yuan Zhang, Benson Chellakkan Selvanesan, Geriolda Topi, Tavga Salim, Janna Sand-Dejmek, Gunilla Jönsson, Anita Sjölander
The inflammatory milieu plays an important role in colon cancer development and progression. Previously, we have shown that tumor-associated macrophages (TAMs), an important component of the tumor microenvironment, are enriched in tumors compared with normal tissue and confer a poorer prognosis. In the present study, we found that matrix metallopeptidase-9 (MMP-9), which degrades extracellular matrix proteins, was increased in biopsies from colon cancer patients and in mouse xenografts with SW480 cell-derived tumors...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28097237/oxidized-camkii-promotes-asthma-through-the-activation-of-mast-cells
#2
Jingjing Qu, Danh C Do, Yufeng Zhou, Elizabeth Luczak, Wayne Mitzner, Mark E Anderson, Peisong Gao
Oxidation of calmodulin-dependent protein kinase II (ox-CaMKII) by ROS has been associated with asthma. However, the contribution of ox-CaMKII to the development of asthma remains to be fully characterized. Here, we tested the effect of ox-CaMKII on IgE-mediated mast cell activation in an allergen-induced mouse model of asthma using oxidant-resistant CaMKII MMVVδ knockin (MMVVδ) mice. Compared with WT mice, the allergen-challenged MMVVδ mice displayed less airway hyperresponsiveness (AHR) and inflammation...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28095362/in-vivo-modulation-of-lps-induced-leukotrienes-generation-and-oxidative-stress-by-sesame-lignans
#3
Puttaraju Srikantamurthy Yashaswini, Bettadahalli Sadashivaiah, Talahalli Ravichandra Ramaprasad, Sridevi Annapurna Singh
The role of inflammation and oxidative stress is critical during onset of metabolic disorders and this has been sufficiently established in literature. In the present study, we evaluated the effects of sesamol and sesamin, two important bioactive molecules present in sesame oil, on the generation of inflammatory and oxidative stress factors in LPS injected rats. Sesamol and sesamin lowered LPS induced expression of cPLA2 (61 and 56%), 5-LOX (44 and 51%), BLT-1(32 and 35%) and LTC4 synthase (49 and 50%), respectively, in liver homogenate...
December 29, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28092287/current-and-future-management-of-the-young-child-with-early-onset-wheezing
#4
Allison J Burbank, Stanley J Szefler
PURPOSE OF REVIEW: In this review, we discuss current thinking in relation to available guidelines for the care of preschool-aged children with recurrent wheezing, while highlighting the gaps in our knowledge and discussing changes that could occur over the next 5 years. RECENT FINDINGS: The Asthma Predictive Index as well as allergen-specific IgE, peripheral eosinophil count and exhaled nitric oxide are perhaps underutilized sources of information that can assist in predicting progression to asthma and response to therapies...
January 13, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28088523/the-selective-cysteinyl-leukotriene-receptor-1-cyslt1r-antagonist-montelukast-regulates-extracellular-matrix-remodeling
#5
Jingli Peng, Hezheng Zhou, Guoping Kuang, Lilian Xie, Tao Tian, Ru Liu
Scar formation after filtration surgery of glaucoma is mainly caused by excessive synthesis of new extracellular matrix (ECM) and contraction of subconjunctival tissue mediated by human Tenon fibroblasts (HTFs) and the transforming growth factor (TGF-β1). Montelukast, a potent and specific cysteinyl leukotriene receptor 1 (cysLT1R) antagonist, is a licensed drug clinically used for the treatment of bronchial asthma. In this study, we investigated the effects of montelukast on the contractility of HTFs cultured in a three-dimensional collagen gel...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28087482/prolonged-acute-suppression-of-cysteinyl-leukotriene-to-reduce-capsular-contracture-around-silicone-implants
#6
Byung Hwi Kim, Min Park, Hyo Jin Park, Seung Ho Lee, Sung Yoon Choi, Chun Gwon Park, Su Min Han, Chan Yeong Heo, Young Bin Choy
: We hypothesize that periodically early, local suppression of cysteinyl leukotrienes (CysLTs), which are potent inflammatory mediators, can reduce the fibrotic capsular contracture around silicone implants. We tested this hypothesis with the silicone implants enabled with the sustained release of montelukast, a CysLT receptor antagonist, for 3 and 15 days. In this work, we inserted each of the distinct implants into the pocket of the subpanniculus carnosus plane of living rats and performed histological and immunofluorescent (IF) analyses of the tissues biopsied at predetermined periods for 12 weeks after implant insertion...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28077599/blt1-mediates-bleomycin-induced-lung-fibrosis-independently-of-neutrophils-and-cd4-t-cells
#7
Jiaoyan Lv, Yingluo Xiong, Wenjing Li, Wei Yang, Lina Zhao, Rui He
Leukotriene B4 (LTB4) and its functional receptor BLT1 are closely involved in tissue inflammation by primarily mediating leukocyte recruitment and activation. Elevated LTB4 was reported in patients with lung fibrosis; however, the role of the LTB4/BLT1 axis in lung fibrosis remains unknown. In this study, we demonstrated that BLT1(-/-) mice exhibited significantly attenuated bleomycin (BLM)-induced lung fibrosis. Interestingly, BLT1 blockade with its specific antagonist U75302 in the acute injury phase (days 0-10 after BLM treatment) significantly attenuated lung fibrosis, which was accompanied by significant decreases in early infiltrating neutrophils and later infiltrating CD4(+) T cells and the production of TGF-β, IL-13, and IL-17A...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28075380/splenic-immune-response-is-down-regulated-in-c57bl-6j-mice-fed-eicosapentaenoic-acid-and-docosahexaenoic-acid-enriched-high-fat-diet
#8
Nikul K Soni, Alastair B Ross, Nathalie Scheers, Otto I Savolainen, Intawat Nookaew, Britt G Gabrielsson, Ann-Sofie Sandberg
Dietary n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with reduction of inflammation, although the mechanisms are poorly understood, especially how the spleen, as a secondary lymphoid organ, is involved. To investigate the effects of EPA and DHA on spleen gene expression, male C57BL/6J mice were fed high fat diets (HFD) differing in fatty acid composition, either based on corn oil (HFD-CO), or CO enriched with 2 g/100 g EPA and DHA (HFD-ED), for eight weeks. Spleen tissue was analyzed using transcriptomics and for fatty acids profiling...
January 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28073701/effect-of-asthma-therapies-on-the-natural-course-of-asthma
#9
REVIEW
Elissa M Abrams, Stanley J Szefler, Allan B Becker
OBJECTIVE: To provide an evidence-based review on the role of pharmacologic (inhaled corticosteroids, leukotriene receptor antagonists, biologic therapies, aeroallergen immunotherapy) and nonpharmacologic therapies (environmental modifications, microbiome) in secondary and tertiary asthma prevention. DATA SOURCES: A PubMed search for English-language publications regarding asthma and secondary or tertiary prevention was performed. Some articles cited in selected studies were also considered for inclusion in this review...
December 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28069825/intravenous-anesthetic-propofol-binds-to-5-lipoxygenase-and-attenuates-leukotriene-b4-production
#10
Toshiaki Okuno, Sophia Koutsogiannaki, Mai Ohba, Matthew Chamberlain, Weiming Bu, Fu-Yan Lin, Roderic G Eckenhoff, Takehiko Yokomizo, Koichi Yuki
Propofol is an intravenous anesthetic that produces its anesthetic effect, largely via the GABAA receptor in the CNS, and also reduces the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophil respiratory burst. Because fMLP-stimulated neutrophils produce leukotriene (LT)B4, we examined the effect of propofol on LTB4 production in vivo and in vitro Cecal ligation and puncture surgery was performed in mice, with or without exposure to propofol. Propofol attenuated the production of 5-lipoxygenase (5-LOX)-related arachidonic acid (AA) derivatives in the peritoneal fluid...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28068410/leukotriene-b%C3%A2-metabolism-and-p70s6-kinase-1-inhibitors-pf-4708671-but-not-ly2584702-inhibits-cyp4f3a-and-the-%C3%AF-oxidation-of-leukotriene-b%C3%A2-in-vitro-and-in-cellulo
#11
Anne-Sophie Archambault, Caroline Turcotte, Cyril Martin, Julie S Lefebvre, Véronique Provost, Michel Laviolette, Nicolas Flamand
LTB4 is an inflammatory lipid mediator mainly biosynthesized by leukocytes. Since its implication in inflammatory diseases is well recognized, many tools to regulate its biosynthesis have been developed and showed promising results in vitro and in vivo, but mixed results in clinical trials. Recently, the mTOR pathway component p70S6 kinase 1 (p70S6K1) has been linked to LTC4 synthase and the biosynthesis of cysteinyl-leukotrienes. In this respect, we investigated if p70S6K1 could also play a role in LTB4 biosynthesis...
2017: PloS One
https://www.readbyqxmd.com/read/28066101/comparison-of-efficacy-safety-and-cost-effectiveness-of-montelukast-levocetirizine-and-montelukast-fexofenadine-in-patients-of-allergic-rhinitis-a-randomized-double-blind-clinical-trial
#12
Mohini Sachin Mahatme, Ganesh Natthuji Dakhale, Kanchan Tadke, Sachin Keshaorao Hiware, S D Dudhgaonkar, Sumit Wankhede
OBJECTIVES: Allergic rhinitis (AR) is a global health problem. Almost 10%-25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene receptor antagonists, and intranasal corticosteroids are the pillars in the management of AR. The combination therapy of montelukast with antihistaminic provides enhancing and complimentary effects, thereby reducing the symptoms effectively, but there are scanty data regarding the comparisons of combinations...
November 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28065501/synthesis-docking-cytotoxicity-and-lta4h-inhibitory-activity-of-new-gingerol-derivatives-as-potential-colorectal-cancer-therapy
#13
Mai H El-Naggar, Amira Mira, Fatma M Abdel Bar, Kuniyoshi Shimizu, Mohamed M Amer, Farid A Badria
Leukotriene A4 hydrolase (LTA4H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene which may play an important role in chronic inflammation associated carcinogenesis. [6]-gingerol, the major bioactive compound of Zingiber officinale, is a potential inhibitor of LTA4H, a highly expressed enzyme in colorectal carcinoma. Eighteen compounds; seven of natural origin (including [4]-, [6]-, [8]-, and [10]-gingerol), five new and six known semi-synthesized [6]-gingerol derivatives were examined using docking, in vitro cytotoxicity against human colon cancer cells (HCT-116) and LTA4H aminopeptidase and epoxide hydrolase inhibitory studies...
December 29, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28063500/cellular-assays-for-evaluating-calcium-dependent-translocation-of-cpla2%C3%AE-to-membrane
#14
B Yun, C C Leslie
The group IVA phospholipase A2, commonly called cytosolic phospholipase A2α (cPLA2α), is a widely expressed enzyme that hydrolyzes membrane phospholipid to produce arachidonic acid and lysophospholipids, which are precursors for a number of bioactive lipid mediators. Arachidonic acid is metabolized through the cyclooxygenase and lipoxygenase pathways for production of prostaglandins and leukotrienes that regulate normal physiological processes and contribute to disease pathogenesis. cPLA2α is composed of an N-terminal C2 domain and a C-terminal catalytic domain that contains the Ser-Asp catalytic dyad...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28058946/evaluation-of-eicosanoid-concentrations-in-stored-units-of-canine-packed-red-blood-cells
#15
Rachel R Blake, Jung Hwa Lee, Matt K Ross, Todd M Archer, Robert W Wills, Andrew J Mackin, John M Thomason
OBJECTIVE To evaluate eicosanoid concentrations in freshly prepared canine packed RBCs (PRBCs) and to assess changes in eicosanoid concentrations in PRBC units over time during storage and under transfusion conditions. DESIGN Prospective study. SAMPLE 25 plasma samples from 14 healthy Greyhounds. PROCEDURES Plasma samples were obtained during PRBC preparation (donation samples), and the PRBC units were then stored at 4°C until used for transfusion (≤ 21 days later; n = 17) or mock transfusion if expired (22 to 24 days later; 8)...
January 15, 2017: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/28057540/low-molecular-weight-heparin-coated-and-montelukast-filled-inhalable-particles-a-dual-drug-delivery-system-for-combination-therapy-in-asthma
#16
Brijeshkumar Patel, Jahidur Rashid, Nilesh Gupta, Fakhrul Ahsan
Montelukast, a cysteinyl leukotriene type 1 receptor antagonist, exhibits secondary anti-inflammatory properties when used at higher concentrations. Low molecular weight heparin (LMWH) evokes pronounced anti-inflammatory effects by interrupting leukocyte adhesion and migration. We hypothesized that inhalable particles containing montelukast plus LMWH release both drugs in a sustained fashion and protect the lungs against allergen-induced inflammation. Large porous particles of montelukast and LMWH were prepared using a double-emulsion-solvent-evaporation method...
January 2, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28053970/leukotriene-b4-levels-in-sputum-from-asthma-patients
#17
Andrew Higham, Paul Cadden, Thomas Southworth, Matthew Rossall, Umme Kolsum, Simon Lea, Richard Knowles, Dave Singh
Poor asthma control is associated with increased airway neutrophils. Leukotriene B4 (LTB4) is a potent neutrophil chemoattractant. We examined the levels of LTB4 levels in the sputum of asthma patients and the relationship with disease severity. 47 asthma patients (categorised according to Global Initiative for Asthma treatment stage) and 12 healthy controls provided sputum samples that were processed first with PBS to obtain supernatants and secondly with dithiothreitol (DTT) to obtain supernatants. LTB4 levels were determined by ELISA...
October 2016: ERJ Open Research
https://www.readbyqxmd.com/read/28049997/self-assessment-of-allergic-rhinitis-and-asthma-sacra-questionnaire-based-allergic-rhinitis-treatment-improves-asthma-control-in-asthmatic-patients-with-allergic-rhinitis
#18
Masanori Yasuo, Yoshiaki Kitaguchi, Yoshimichi Komatsu, Mineyuki Hama, Tomonobu Koizumi, Toshihiko Agatsuma, Takashi Ichiyama, Akane Kato, Hideaki Moteki, Masayuki Hanaoka
Objective This study was conducted to investigate whether the add-on treatment of allergic rhinitis (AR) based on the Self-assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire for assessing AR control improves both AR and asthma control in asthmatic patients with AR. Methods This multi-center prospective study was performed in Nagano prefecture, Japan. Two hundred five asthmatic patients and 23 respiratory physicians participated in the study. We administered add-on AR treatments based on the results of the SACRA questionnaire...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28046032/inflammatory-mediators-in-tracheal-aspirates-of-preterm-infants-participating-in-a-randomized-trial-of-inhaled-nitric-oxide
#19
Mandy Laube, Elena Amann, Ulrike Uhlig, Yang Yang, Hans W Fuchs, Michael Zemlin, Jean-Christophe Mercier, Rolf F Maier, Helmut D Hummler, Stefan Uhlig, Ulrich H Thome
BACKGROUND: Ventilated preterm infants frequently develop bronchopulmonary dysplasia (BPD) which is associated with elevated inflammatory mediators in their tracheal aspirates (TA). In animal models of BPD, inhaled nitric oxide (iNO) has been shown to reduce lung inflammation, but data for human preterm infants is missing. METHODS: Within a European multicenter trial of NO inhalation for preterm infants to prevent BPD (EUNO), TA was collected to determine the effects of iNO on pulmonary inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28036068/design-synthesis-and-cellular-characterization-of-a-dual-inhibitor-of-5-lipoxygenase-and-soluble-epoxide-hydrolase
#20
Karin Meirer, Daniel Glatzel, Simon Kretschmer, Sandra K Wittmann, Markus Hartmann, René Blöcher, Carlo Angioni, Gerd Geisslinger, Dieter Steinhilber, Bettina Hofmann, Robert Fürst, Ewgenij Proschak
The arachidonic acid cascade is a key player in inflammation, and numerous well-established drugs interfere with this pathway. Previous studies have suggested that simultaneous inhibition of 5-lipoxygenase (5-LO) and soluble epoxide hydrolase (sEH) results in synergistic anti-inflammatory effects. In this study, a novel prototype of a dual 5-LO/sEH inhibitor KM55 was rationally designed and synthesized. KM55 was evaluated in enzyme activity assays with recombinant enzymes. Furthermore, activity of KM55 in human whole blood and endothelial cells was investigated...
December 29, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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