leukotrienes

Summary

Summary: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.

Top Publications

  1. Rogerio A, Anibal F. Role of leukotrienes on protozoan and helminth infections. Mediators Inflamm. 2012;2012:595694 pubmed publisher
    b>Leukotrienes (LTs), formed by the 5-lipoxygenase-(5-LO-) catalyzed oxidation of arachidonic acid, are lipid mediators that have potent proinflammatory activities...
  2. Neves J, Radke A, Weller P. Cysteinyl leukotrienes acting via granule membrane-expressed receptors elicit secretion from within cell-free human eosinophil granules. J Allergy Clin Immunol. 2010;125:477-82 pubmed publisher
    Cysteinyl leukotrienes (cysLTs) are recognized to act via receptors (cysLTRs) expressed on cell surface plasma membranes. Agents that block cysLT(1) receptor (cysLT(1)R) are therapeutics for allergic disorders...
  3. Tufvesson E, Bozovic G, Hesselstrand R, Bjermer L, Scheja A, Wuttge D. Increased cysteinyl-leukotrienes and 8-isoprostane in exhaled breath condensate from systemic sclerosis patients. Rheumatology (Oxford). 2010;49:2322-6 pubmed publisher
    ..The fibrotic process is believed to be influenced by leukotrienes (LTs) and also by oxidative stress...
  4. Bäck M. Inflammatory signaling through leukotriene receptors in atherosclerosis. Curr Atheroscler Rep. 2008;10:244-51 pubmed
    The atherosclerotic lesion is a site of local production of the lipid-derived inflammatory mediators known as leukotrienes. This production leads to autocrine and paracrine activation of leukotriene receptors of the BLT and CysLT receptor ..
  5. Montuschi P. Leukotrienes, antileukotrienes and asthma. Mini Rev Med Chem. 2008;8:647-56 pubmed
    b>Leukotrienes (LTs), including LTB(4) and cysteinyl-LTs (CysLTs) (LTC(4), LTD(4), and LTE(4)), are potent inflammatory lipid mediators which are derived from 5-lipoxygenase activity...
  6. Wright M, Piedimonte G. Respiratory syncytial virus prevention and therapy: past, present, and future. Pediatr Pulmonol. 2011;46:324-47 pubmed publisher
  7. Foster H, Fuerst E, Lee T, Cousins D, Woszczek G. Characterisation of P2Y(12) receptor responsiveness to cysteinyl leukotrienes. PLoS ONE. 2013;8:e58305 pubmed publisher
    Leukotriene E4 (LTE4), the most stable of the cysteinyl leukotrienes (cysLTs), binds poorly to classical type 1 and 2 cysLT receptors although in asthmatic individuals it may potently induce bronchial constriction, airway ..
  8. Giouleka P, Papatheodorou G, Lyberopoulos P, Karakatsani A, Alchanatis M, Roussos C, et al. Body mass index is associated with leukotriene inflammation in asthmatics. Eur J Clin Invest. 2011;41:30-8 pubmed publisher
    ..Alterations of leptin/adiponectin balance may be related to the presence of leukotriene inflammation in obese asthmatic patients. ..
  9. Wu S, Yin P, Zhang Y, Tao H. Reversed changes of lipoxin A4 and leukotrienes in children with asthma in different severity degree. Pediatr Pulmonol. 2010;45:333-40 pubmed publisher

More Information

Publications62

  1. Duroudier N, Tulah A, Sayers I. Leukotriene pathway genetics and pharmacogenetics in allergy. Allergy. 2009;64:823-39 pubmed publisher
    b>Leukotrienes (LT) are biologically active lipid mediators known to be involved in allergic inflammation...
  2. Talahalli R, Zarini S, Tang J, Li G, Murphy R, Kern T, et al. Leukocytes regulate retinal capillary degeneration in the diabetic mouse via generation of leukotrienes. J Leukoc Biol. 2013;93:135-43 pubmed publisher
    ..05). Our data suggest the critical involvement of leukocytes and LTs in the regulation of inflammation and capillary degeneration in DR. ..
  3. Parmentier C, Fuerst E, McDonald J, Bowen H, Lee T, Pease J, et al. Human T(H)2 cells respond to cysteinyl leukotrienes through selective expression of cysteinyl leukotriene receptor 1. J Allergy Clin Immunol. 2012;129:1136-42 pubmed publisher
    ..Cysteinyl leukotrienes (CysLTs) are potent lipid mediators involved in bronchoconstriction, mucus secretion, and cell trafficking in ..
  4. Mandal A, Jones P, Bair A, Christmas P, Miller D, Yamin T, et al. The nuclear membrane organization of leukotriene synthesis. Proc Natl Acad Sci U S A. 2008;105:20434-9 pubmed publisher
    b>Leukotrienes (LTs) are signaling molecules derived from arachidonic acid that initiate and amplify innate and adaptive immunity...
  5. Haeggstrom J, Rinaldo Matthis A, Wheelock C, Wetterholm A. Advances in eicosanoid research, novel therapeutic implications. Biochem Biophys Res Commun. 2010;396:135-9 pubmed publisher
    ..are a family of oxygenated metabolites of arachidonic acid, including the prostaglandins, thromboxanes, leukotrienes and lipoxins...
  6. Yan D, Stocco R, Sawyer N, Nesheim M, Abramovitz M, Funk C. Differential signaling of cysteinyl leukotrienes and a novel cysteinyl leukotriene receptor 2 (CysLT?) agonist, N-methyl-leukotriene C?, in calcium reporter and ? arrestin assays. Mol Pharmacol. 2011;79:270-8 pubmed publisher
    The cysteinyl leukotrienes (cysLTs) LTC?, LTD?, and LTE? are lipid mediators with physiological and pathophysiological functions...
  7. Boudreau L, Bertin J, Robichaud P, Laflamme M, Ouellette R, Flamand N, et al. Novel 5-lipoxygenase isoforms affect the biosynthesis of 5-lipoxygenase products. FASEB J. 2011;25:1097-105 pubmed publisher
    5-Lipoxygenase (5-LO) is the essential enzyme for the biosynthesis of leukotrienes, important mediators of inflammation. This study investigated whether variants of 5-LO exist in human leukocytes...
  8. Riccioni G, Bäck M, Capra V. Leukotrienes and atherosclerosis. Curr Drug Targets. 2010;11:882-7 pubmed
    Evidence from experimental and genetic studies suggest the existence of a potential link between the leukotrienes (LT) signalling cascade, and the pathogenesis/progression of atherosclerosis and its serious consequences such as acute ..
  9. Panis C, Mazzuco T, Costa C, Victorino V, Tatakihara V, Yamauchi L, et al. Trypanosoma cruzi: effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide and iNOS expression in cardiac tissue in the acute phase of infection in mice. Exp Parasitol. 2011;127:58-65 pubmed publisher
    b>Leukotrienes are important mediators of inflammatory responses...
  10. Sala A, Folco G, Murphy R. Transcellular biosynthesis of eicosanoids. Pharmacol Rep. 2010;62:503-10 pubmed
    ..review will summarize the evidence for transcellular biosynthetic events, occurring in isolated cell preparations, complex isolated organ systems, and in vivo, that result in the production of prostaglandins, leukotrienes, and lipoxins.
  11. Paiva L, Maya Monteiro C, Bandeira Melo C, Silva P, El Cheikh M, Teodoro A, et al. Interplay of cysteinyl leukotrienes and TGF-? in the activation of hepatic stellate cells from Schistosoma mansoni granulomas. Biochim Biophys Acta. 2010;1801:1341-8 pubmed publisher
    ..Here, we investigated the interplay between leukotrienes (LT) and TGF-? in the activation mechanisms of HSCs from schistosomal granulomas (GR-HSCs)...
  12. Pugliese A, Trincavelli M, Lecca D, Coppi E, Fumagalli M, Ferrario S, et al. Functional characterization of two isoforms of the P2Y-like receptor GPR17: [35S]GTPgammaS binding and electrophysiological studies in 1321N1 cells. Am J Physiol Cell Physiol. 2009;297:C1028-40 pubmed publisher
    ..receptor GPR17 is structurally related to both P2Y nucleotide receptors and to receptors for cysteinyl leukotrienes. Genomic analysis revealed two putative open reading frames encoding for a "short" and a "long&..
  13. Ichiyama T, Hasegawa M, Hashimoto K, Matsushige T, Hirano R, Furukawa S. Cysteinyl leukotrienes induce macrophage inflammatory protein-1 in human monocytes/macrophages. Int Arch Allergy Immunol. 2009;148:147-53 pubmed publisher
    ..CysLTs induce MIP-1alpha and MIP-1beta production mediated by ERK via binding to the CysLT(1) receptor in human monocytes/macrophages. ..
  14. Noguchi K, Okubo M. Leukotrienes in nociceptive pathway and neuropathic/inflammatory pain. Biol Pharm Bull. 2011;34:1163-9 pubmed
    The purpose of this review is to summarize the recent studies examining the expression of leukotrienes (LTs) and their receptors in nociceptive pathways, and their crucial roles in pathological pain conditions...
  15. Hallstrand T, Henderson W. Role of leukotrienes in exercise-induced bronchoconstriction. Curr Allergy Asthma Rep. 2009;9:18-25 pubmed
    ..b>Leukotrienes (LTs) play a critical role in the pathophysiology of EIB...
  16. Israel E. The protective effects of leukotriene modifiers in aspirin-induced asthma. Postgrad Med. 2000;108:40-4 pubmed publisher
    ..and the leukotriene receptor antagonists (LTRAs)--have established the critical pathogenic role played by leukotrienes in aspirin-induced asthma (AIA)...
  17. Evans J, Ferguson A, Mosley R, Hutchinson J. What's all the FLAP about?: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases. Trends Pharmacol Sci. 2008;29:72-8 pubmed publisher
    b>Leukotrienes have physiological roles in innate immune responses and pathological roles in inflammatory diseases, such as asthma, allergic rhinitis and atherosclerosis...
  18. Jawien J, Korbut R. The current view on the role of leukotrienes in atherogenesis. J Physiol Pharmacol. 2010;61:647-50 pubmed
  19. Barrett N, Rahman O, Fernandez J, Parsons M, Xing W, Austen K, et al. Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes. J Exp Med. 2011;208:593-604 pubmed publisher
    ..These findings identify a previously unrecognized link between a myeloid C-type lectin receptor and Th2 immunity. ..
  20. Chakrabarti S, Cole B, Wen Y, Keller S, Nadler J. 12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes. Obesity (Silver Spring). 2009;17:1657-63 pubmed publisher
  21. Zarini S, Gijón M, Ransome A, Murphy R, Sala A. Transcellular biosynthesis of cysteinyl leukotrienes in vivo during mouse peritoneal inflammation. Proc Natl Acad Sci U S A. 2009;106:8296-301 pubmed publisher
    b>Leukotrienes (LTs) are lipid mediators of inflammation formed by enzymatic oxidation of arachidonic acid...
  22. Hersberger M. Potential role of the lipoxygenase derived lipid mediators in atherosclerosis: leukotrienes, lipoxins and resolvins. Clin Chem Lab Med. 2010;48:1063-73 pubmed publisher
    ..a role in leukocyte recruitment through the generation of two classes of arachidonic acid lipid mediators, the leukotrienes and the lipoxins, and one class of omega-3 fatty acid metabolites, the resolvins...
  23. Bäck M. Leukotriene signaling in atherosclerosis and ischemia. Cardiovasc Drugs Ther. 2009;23:41-8 pubmed publisher
    ..by phospholipase A(2) serves as substrate for the production of a group of lipid mediators known as the leukotrienes, which induce pro-inflammatory signaling through activation of specific BLT and CysLT receptors...
  24. Cao R, St Amand T, Grabner R, Habenicht A, Funk C. Genetic and pharmacological inhibition of the 5-lipoxygenase/leukotriene pathway in atherosclerotic lesion development in ApoE deficient mice. Atherosclerosis. 2009;203:395-400 pubmed publisher
    ..These results do not support a role for the 5-LO/LT pathway in intermediate to advanced atherosclerotic lesion development in mice. ..
  25. Hikiji H, Takato T, Shimizu T, Ishii S. The roles of prostanoids, leukotrienes, and platelet-activating factor in bone metabolism and disease. Prog Lipid Res. 2008;47:107-26 pubmed publisher
    ..The multifaceted nature of PGE(2) makes it difficult to discern its role during bone remodeling. Leukotrienes (LTs), and particularly LTB(4), have also been implicated in bone remodeling and disease-specifically in ..
  26. Martínez Clemente M, Claria J, Titos E. The 5-lipoxygenase/leukotriene pathway in obesity, insulin resistance, and fatty liver disease. Curr Opin Clin Nutr Metab Care. 2011;14:347-53 pubmed publisher
    ..discusses recent data implicating lipoxygenases and especially 5-lipoxygenase and its derived products, the leukotrienes, in mounting adipose tissue inflammation and related pathologies in obesity...
  27. Mothe Satney I, Filloux C, Amghar H, Pons C, Bourlier V, Galitzky J, et al. Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin resistance in mice. Diabetes. 2012;61:2311-9 pubmed publisher
    b>Leukotrienes (LTs) are potent proinflammatory mediators, and many important aspects of innate and adaptive immune responses are regulated by LTs...
  28. Riccioni G, Zanasi A, Vitulano N, Mancini B, D Orazio N. Leukotrienes in atherosclerosis: new target insights and future therapy perspectives. Mediators Inflamm. 2009;2009:737282 pubmed publisher
    ..by phospholipase A2, is an important substrate for the production of a group of lipid mediators known as leukotrienes, which induce proinflammatory signaling through the activation of specific BLT and CysLT receptors...
  29. Farias S, Frey L, Murphy R, Heidenreich K. Injury-related production of cysteinyl leukotrienes contributes to brain damage following experimental traumatic brain injury. J Neurotrauma. 2009;26:1977-86 pubmed publisher
    The leukotrienes belong to a family of biologically active lipids derived from arachidonate that are often involved in inflammatory responses...
  30. Drakatos P, Lykouras D, Sampsonas F, Karkoulias K, Spiropoulos K. Targeting leukotrienes for the treatment of COPD?. Inflamm Allergy Drug Targets. 2009;8:297-306 pubmed
    ..Also cysteinyl leukotrienes (LTC4, LTD4 and LTE4) are known to induce mucus secretion, inflammatory cell infiltration, increase vascular ..
  31. Bäck M, Dahlen S, Drazen J, Evans J, Serhan C, Shimizu T, et al. International Union of Basic and Clinical Pharmacology. LXXXIV: leukotriene receptor nomenclature, distribution, and pathophysiological functions. Pharmacol Rev. 2011;63:539-84 pubmed publisher
    The seven-transmembrane G protein-coupled receptors activated by leukotrienes are divided into two subclasses based on their ligand specificity for either leukotriene B(4) or the cysteinyl leukotrienes (LTC(4), LTD(4), and LTE(4))...
  32. Tufvesson E, van Weele L, Ekedahl H, Bjermer L. Levels of cysteinyl-leukotrienes in exhaled breath condensate are not due to saliva contamination. Clin Respir J. 2010;4:83-8 pubmed publisher
    Saliva contamination has been suggested to be a major contributor to levels of cysteinyl leukotrienes in exhaled breath condensate (EBC)...
  33. Mishra N, Rir Sima Ah J, Boyd R, Singh S, Gundavarapu S, Langley R, et al. Nicotine inhibits Fc epsilon RI-induced cysteinyl leukotrienes and cytokine production without affecting mast cell degranulation through alpha 7/alpha 9/alpha 10-nicotinic receptors. J Immunol. 2010;185:588-96 pubmed publisher
    ..Cysteinyl leukotrienes are primarily produced by mast cells, and these cells play a central role in allergic asthma...
  34. Hallstrand T, Henderson W. An update on the role of leukotrienes in asthma. Curr Opin Allergy Clin Immunol. 2010;10:60-6 pubmed publisher
    b>Leukotrienes are lipid mediators involved in the pathogenesis of asthma. There is significant new information about the actions of leukotrienes in asthma and the evolving role of antileukotriene therapies...
  35. Ono E, Taniguchi M, Mita H, Fukutomi Y, Higashi N, Miyazaki E, et al. Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxis. Clin Exp Allergy. 2009;39:72-80 pubmed publisher
    ..Urinary LTE4 and 9alpha, 11beta-PGF2 concentrations may be a reliable marker of endogenous production of inflammatory mediators associated with anaphylaxis. ..
  36. Gaber F, Daham K, Higashi A, Higashi N, Gülich A, Delin I, et al. Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma. Thorax. 2008;63:1076-82 pubmed publisher
    ..was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B(4) (LTB(4)) in saliva, sputum and ex vivo stimulated blood in subjects with aspirin-..
  37. Eap R, Jacques E, Semlali A, Plante S, Chakir J. Cysteinyl leukotrienes regulate TGF-?(1) and collagen production by bronchial fibroblasts obtained from asthmatic subjects. Prostaglandins Leukot Essent Fatty Acids. 2012;86:127-33 pubmed publisher
    Cysteinyl leukotrienes (CysLTs) play an important role in airway inflammation in asthma but their role in airway remodeling is not completely known. CysLTs receptors and procollagen I(?(1)) mRNA were determined by qPCR...
  38. Niimi A. Cough, asthma, and cysteinyl-leukotrienes. Pulm Pharmacol Ther. 2013;26:514-9 pubmed publisher
    ..Cyteinyl-leukotrienes (cys-LTs) are one of the chemical mediators that play major pathophysiological roles in asthma...
  39. Faith A, Fernandez M, Caulfield J, Loke T, Corrigan C, O CONNOR B, et al. Role of cysteinyl leukotrienes in human allergen-specific Th2 responses induced by granulocyte macrophage-colony stimulating factor. Allergy. 2008;63:168-75 pubmed publisher
    ..Novel immunotherapies, targeting production of GM-CSF or its actions on APC have the potential, therefore, to prove beneficial in treatment of patients with inflammatory airway disease. ..
  40. Ochkur S, Protheroe C, Li W, Colbert D, Zellner K, Shen H, et al. Cys-leukotrienes promote fibrosis in a mouse model of eosinophil-mediated respiratory inflammation. Am J Respir Cell Mol Biol. 2013;49:1074-84 pubmed publisher
    b>Leukotrienes (i.e., products of the 5-lipoxygenase pathway) are thought to be contributors to lung pathologies...
  41. Di Gennaro A, Wågsäter D, Mäyränpää M, Gabrielsen A, Swedenborg J, Hamsten A, et al. Increased expression of leukotriene C4 synthase and predominant formation of cysteinyl-leukotrienes in human abdominal aortic aneurysm. Proc Natl Acad Sci U S A. 2010;107:21093-7 pubmed publisher
    b>Leukotrienes (LTs) are arachidonic acid-derived lipid mediators involved in the pathogenesis and progression of diverse inflammatory disorders...
  42. Okunishi K, Peters Golden M. Leukotrienes and airway inflammation. Biochim Biophys Acta. 2011;1810:1096-102 pubmed publisher
    ..b>Leukotrienes (LTs) are lipid mediators that contribute to many aspects of asthma pathogenesis...
  43. Barajas Espinosa A, Ni N, Yan D, Zarini S, Murphy R, Funk C. The cysteinyl leukotriene 2 receptor mediates retinal edema and pathological neovascularization in a murine model of oxygen-induced retinopathy. FASEB J. 2012;26:1100-9 pubmed publisher
    b>Leukotrienes have been implicated in the pathogenesis of degenerative diabetic retinopathy, with research focusing primarily on leukotriene B(4), with little attention devoted to the cysteinyl leukotrienes (cysLTs), which act through ..
  44. Poeckel D, Funk C. The 5-lipoxygenase/leukotriene pathway in preclinical models of cardiovascular disease. Cardiovasc Res. 2010;86:243-53 pubmed publisher
    b>Leukotrienes (LTs) derived from 5-lipoxygenase (5-LO) activity are most widely known for their actions during acute inflammation and asthma...
  45. Van Ly D, Burgess J, Brock T, Lee T, Black J, Oliver B. Prostaglandins but not leukotrienes alter extracellular matrix protein deposition and cytokine release in primary human airway smooth muscle cells and fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2012;303:L239-50 pubmed publisher
    ..Increasing evidence suggests that eicosanoids such as leukotrienes and prostaglandins (PGs) may directly mediate remodeling...
  46. Jawien J. The putative role of leukotrienes in experimental atherogenesis. Pol Arch Med Wewn. 2009;119:90-3 pubmed
    ..The article also discusses the importance of these findings for the future use in the clinic. ..
  47. Moos M, Funk C. Endothelial cysteinyl leukotriene 2 receptor expression and myocardial ischemia/reperfusion injury. Trends Cardiovasc Med. 2008;18:268-73 pubmed publisher
    ..Cysteinyl leukotrienes are well known lipid mediators of inflammation...
  48. Bevan S, Dichgans M, Wiechmann H, Gschwendtner A, Meitinger T, Markus H. Genetic variation in members of the leukotriene biosynthesis pathway confer an increased risk of ischemic stroke: a replication study in two independent populations. Stroke. 2008;39:1109-14 pubmed publisher
    ..665; P=0.013). Genetic variation in leukotriene pathway members and their receptors confer an increased risk of ischemic stroke in 2 independent populations. These risks show different magnitudes depending on ischemic stroke subtype. ..
  49. Petersen B, Austen K, Bloch K, Hotta Y, Ichinose F, Kanaoka Y, et al. Cysteinyl leukotrienes impair hypoxic pulmonary vasoconstriction in endotoxemic mice. Anesthesiology. 2011;115:804-11 pubmed publisher
    ..Concentrations of cysteinyl leukotrienes are increased in the bronchoalveolar lavage fluid of patients with sepsis, but the contribution of cysteinyl ..
  50. Han J, Jia Y, Takeda K, Shiraishi Y, Okamoto M, Dakhama A, et al. Montelukast during primary infection prevents airway hyperresponsiveness and inflammation after reinfection with respiratory syncytial virus. Am J Respir Crit Care Med. 2010;182:455-63 pubmed publisher
    ..These data support an important role for cysLT in RSV-induced AHR and inflammation. ..
  51. Riccioni G, Bäck M. Leukotrienes as modifiers of preclinical atherosclerosis?. ScientificWorldJournal. 2012;2012:490968 pubmed publisher
    ..including high-sensitivity C-reactive protein, cell adhesion molecules and matrix metalloproteinases, and leukotrienes. Recently, leukotrienes have been implicated as mediators, biomarkers, and possible therapeutic targets in the ..
  52. Barrett N, Maekawa A, Rahman O, Austen K, Kanaoka Y. Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells. J Immunol. 2009;182:1119-28 pubmed
    ..pteronyssinus and from the mold Aspergillus fumigatus stimulated a rapid and robust production of cysteinyl leukotrienes (cys-LTs), proinflammatory lipid mediators, from mouse bone marrow-derived dendritic cells (BMDCs)...
  53. Schain F, Tryselius Y, Sjoberg J, Porwit A, Backman L, Malec M, et al. Evidence for a pathophysiological role of cysteinyl leukotrienes in classical Hodgkin lymphoma. Int J Cancer. 2008;123:2285-93 pubmed publisher
    ..Here, we present data that link inflammatory cell-derived arachidonic acid metabolites, the cysteinyl leukotrienes (CysLT), to the pathogenesis of cHL...