Alox5

Summary

Gene Symbol: Alox5
Description: arachidonate 5-lipoxygenase
Alias: 5-LO, 5-LOX, 5LO, 5LX, AI850497, F730011J02, arachidonate 5-lipoxygenase, 5-lipoxygenase
Species: mouse
Products:     Alox5

Top Publications

  1. Medeiros A, Sa Nunes A, Turato W, Secatto A, Frantz F, Sorgi C, et al. Leukotrienes are potent adjuvant during fungal infection: effects on memory T cells. J Immunol. 2008;181:8544-51 pubmed
    ..These data establish an important immunomodulatory role of LTs, in both the primary and secondary immune responses to histoplasmosis. ..
  2. Queto T, Gaspar Elsas M, Masid de Brito D, Vasconcelos Z, Ferraris F, Penido C, et al. Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow. J Leukoc Biol. 2010;87:885-93 pubmed publisher
    ..These findings provide evidence for: a) a novel role of eotaxin and IL-13 in regulating eosinophilopoiesis; and b) a role for CysLTRs in bone marrow cells in transducing cytokine regulatory signals. ..
  3. Serezani C, Aronoff D, Jancar S, Mancuso P, Peters Golden M. Leukotrienes enhance the bactericidal activity of alveolar macrophages against Klebsiella pneumoniae through the activation of NADPH oxidase. Blood. 2005;106:1067-75 pubmed
    ..Our results demonstrate that LTs, especially LTB4, enhanceAM microbicidal activity through the PKC-delta-dependent activation of NADPH oxidase. ..
  4. Bafica A, Scanga C, Serhan C, Machado F, White S, Sher A, et al. Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production. J Clin Invest. 2005;115:1601-6 pubmed
    ..tuberculosis. ..
  5. Serezani C, Perrela J, Russo M, Peters Golden M, Jancar S. Leukotrienes are essential for the control of Leishmania amazonensis infection and contribute to strain variation in susceptibility. J Immunol. 2006;177:3201-8 pubmed
    ..amazonensis, identify relevant leishmanicidal mechanisms, and suggest that genetic variation in LTB4 synthesis might influence resistance and susceptibility patterns to infection. ..
  6. Verri W, Cunha T, Ferreira S, Wei X, Leung B, Fraser A, et al. IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. Eur J Immunol. 2007;37:3373-80 pubmed
  7. Gubitosi Klug R, Talahalli R, Du Y, Nadler J, Kern T. 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes. 2008;57:1387-93 pubmed publisher
    ..5-Lipoxygenase represents a novel pathway for therapeutic intervention of diabetic retinopathy. ..
  8. Pavanelli W, Gutierrez F, Mariano F, Prado C, Ferreira B, Teixeira M, et al. 5-lipoxygenase is a key determinant of acute myocardial inflammation and mortality during Trypanosoma cruzi infection. Microbes Infect. 2010;12:587-97 pubmed publisher
    ..These results show that efficient parasite clearance is possible in a context of moderate inflammatory response, as occurred in 5-LO(-/-) mice, in which reduced myocarditis protects the animals during T. cruzi infection. ..
  9. Serezani C, Lewis C, Jancar S, Peters Golden M. Leukotriene B4 amplifies NF-?B activation in mouse macrophages by reducing SOCS1 inhibition of MyD88 expression. J Clin Invest. 2011;121:671-82 pubmed publisher
    ..These results uncover a pivotal role in macrophages for the GPCR BLT1 in regulating activation of NF-?B through Stat1-dependent expression of MyD88. ..

More Information

Publications83

  1. Sadik C, Kim N, Iwakura Y, Luster A. Neutrophils orchestrate their own recruitment in murine arthritis through C5aR and Fc?R signaling. Proc Natl Acad Sci U S A. 2012;109:E3177-85 pubmed publisher
  2. Tristão F, Rocha F, Moreira A, Cunha F, Rossi M, Silva J. 5-Lipoxygenase activity increases susceptibility to experimental Paracoccidioides brasiliensis infection. Infect Immun. 2013;81:1256-66 pubmed publisher
    ..Taken together, our results show for the first time that 5-LO enzymatic activity increases susceptibility to P. brasiliensis, suggesting that this pathway may be a potential target for therapeutic intervention during PCM...
  3. Chen X, Naumann T, Kurre U, Jenkins N, Copeland N, Funk C. cDNA cloning, expression, mutagenesis, intracellular localization, and gene chromosomal assignment of mouse 5-lipoxygenase. J Biol Chem. 1995;270:17993-9 pubmed
    ..These studies provide a global picture of the murine 5-lipoxygenase system and raise questions about the role of 5-lipoxygenase and leukotrienes within the nucleus. ..
  4. Goulet J, Snouwaert J, Latour A, Coffman T, Koller B. Altered inflammatory responses in leukotriene-deficient mice. Proc Natl Acad Sci U S A. 1994;91:12852-6 pubmed
    ..we describe the phenotypic analysis of leukotriene-deficient mice generated by inactivation of the 5-lipoxygenase (5LO) gene...
  5. Chen Y, Hu Y, Zhang H, Peng C, Li S. Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia. Nat Genet. 2009;41:783-92 pubmed publisher
    ..Here we identify the arachidonate 5-lipoxygenase (5-LO) gene (Alox5) as a critical regulator for leukemia stem cells (LSCs) in BCR-ABL-induced chronic myeloid leukemia (CML)...
  6. Monteiro A, Pinheiro C, Luna Gomes T, Alves L, Maya Monteiro C, Porto B, et al. Leukotriene B4 mediates neutrophil migration induced by heme. J Immunol. 2011;186:6562-7 pubmed publisher
  7. Serezani C, Kane S, Collins L, Morato Marques M, Osterholzer J, Peters Golden M. Macrophage dectin-1 expression is controlled by leukotriene B4 via a GM-CSF/PU.1 axis. J Immunol. 2012;189:906-15 pubmed publisher
    ..Our results identify LTB(4)-BLT1 signaling as an unrecognized controller of dectin-1 transcription via GM-CSF and PU.1 that is required for fungi-protective host responses. ..
  8. Serezani C, Aronoff D, Jancar S, Peters Golden M. Leukotriene B4 mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acid-stimulated neutrophils. J Leukoc Biol. 2005;78:976-84 pubmed
    ..These results identify a heretofore unrecognized role for activation of 5-LO and subsequent production of LTB(4) in stimulation of PMN NADPH oxidase activation by PUFAs. ..
  9. Bailie M, Standiford T, Laichalk L, Coffey M, Strieter R, Peters Golden M. Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities. J Immunol. 1996;157:5221-4 pubmed
    ..We conclude that endogenous LTs play a critical role in the defense against bacterial pneumonia in this murine model. ..
  10. Chen X, Sheller J, Johnson E, Funk C. Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene. Nature. 1994;372:179-82 pubmed
    ..5-Lipoxygenase-deficient (5LX-/-) mice develop normally and are healthy. They show a selective opposition to certain inflammatory insults...
  11. Chu J, Pratico D. Pharmacologic blockade of 5-lipoxygenase improves the amyloidotic phenotype of an Alzheimer's disease transgenic mouse model involvement of ?-secretase. Am J Pathol. 2011;178:1762-9 pubmed publisher
    ..They suggest that pharmacological inhibition of 5-LO could provide a novel therapeutic opportunity for AD. ..
  12. Mehrabian M, Allayee H, Stockton J, Lum P, Drake T, Castellani L, et al. Integrating genotypic and expression data in a segregating mouse population to identify 5-lipoxygenase as a susceptibility gene for obesity and bone traits. Nat Genet. 2005;37:1224-33 pubmed
  13. Chen M, Lam B, Kanaoka Y, Nigrovic P, Audoly L, Austen K, et al. Neutrophil-derived leukotriene B4 is required for inflammatory arthritis. J Exp Med. 2006;203:837-42 pubmed
    ..These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption. ..
  14. Silverman E, Le L, Baron R, Hallock A, Hjoberg J, Shikanai T, et al. Cloning and functional analysis of the mouse 5-lipoxygenase promoter. Am J Respir Cell Mol Biol. 2002;26:475-83 pubmed
    5-lipoxygenase (ALOX5), an enzyme essential for the formation of all leukotrienes, is highly regulated at multiple levels, including gene transcription. The human ALOX5 promoter sequence has been cloned and is well characterized...
  15. Patnode M, Bando J, Krummel M, Locksley R, Rosen S. Leukotriene B4 amplifies eosinophil accumulation in response to nematodes. J Exp Med. 2014;211:1281-8 pubmed publisher
    ..The similarity of the eosinophil responses to diverse nematode species suggests that conserved features of nematodes are recognized during parasite infection. ..
  16. Mehrabian M, Schulthess F, Nebohacova M, Castellani L, Zhou Z, Hartiala J, et al. Identification of ALOX5 as a gene regulating adiposity and pancreatic function. Diabetologia. 2008;51:978-88 pubmed publisher
    We previously used an integrative genetics approach to demonstrate that 5-lipoxygenase (5-LO) deficiency in mice (Alox5 (-/-)) protects against atherosclerosis despite increasing lipid levels and fat mass...
  17. Uz T, Dimitrijevic N, Imbesi M, Manev H, Manev R. Effects of MK-886, a 5-lipoxygenase activating protein (FLAP) inhibitor, and 5-lipoxygenase deficiency on the forced swimming behavior of mice. Neurosci Lett. 2008;436:269-72 pubmed publisher
    ..Increased activity of the enzymatic 5-lipoxygenase (5-LOX, 5LO) pathway is a contributing factor in atherosclerosis and a 5-LOX inhibitor, MK-886, is beneficial in animal models ..
  18. Firuzi O, Zhuo J, Chinnici C, Wisniewski T, Pratico D. 5-Lipoxygenase gene disruption reduces amyloid-beta pathology in a mouse model of Alzheimer's disease. FASEB J. 2008;22:1169-78 pubmed
    5-Lipoxygenase (5LO), by producing leukotrienes, is a proinflammatory enzyme, and there is evidence suggesting that it is up-regulated with aging and may be involved in Alzheimer's disease (AD)...
  19. Goulet J, Griffiths R, Ruiz P, Mannon R, Flannery P, Platt J, et al. Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice. J Immunol. 2001;167:6631-6 pubmed
    ..we transplanted kidneys from CByD2F1 mice into fully allogeneic 129 mice that carry a targeted mutation in the 5lo gene...
  20. Mancuso P, Lewis C, Serezani C, Goel D, Peters Golden M. Intrapulmonary administration of leukotriene B4 enhances pulmonary host defense against pneumococcal pneumonia. Infect Immun. 2010;78:2264-71 pubmed publisher
    ..The results of the current study in an animal model serve as a proof of concept for the potential utility of treatment with aerosolized LTB(4) as an immunostimulatory strategy in patients with bacterial pneumonia...
  21. Secatto A, Rodrigues L, Serezani C, Ramos S, Dias Baruffi M, Faccioli L, et al. 5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection. PLoS ONE. 2012;7:e31701 pubmed publisher
    ..Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis. ..
  22. Peng C, Chen Y, Shan Y, Zhang H, Guo Z, Li D, et al. LSK derived LSK- cells have a high apoptotic rate related to survival regulation of hematopoietic and leukemic stem cells. PLoS ONE. 2012;7:e38614 pubmed publisher
    ..is reduced in CML mice, and depletion of leukemia stem cells (LSCs; BCR-ABL-expressing HSCs) by deleting Alox5 or by inhibiting heat shock protein 90 causes an increase in this LSK(-) population...
  23. Green J, Stockton R, Johnson C, Jacobson B. 5-lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers. Am J Physiol Cell Physiol. 2004;287:C373-83 pubmed
    ..These data suggest that two competing oxidative enzymes in arachidonate metabolism, LOX and COX, differentially regulate sequential aspects of fibroblast wound closure in vitro. ..
  24. Lee S, Choi E, Seo K, Bae J, Kim Y, Park S, et al. 5-Lipoxygenase plays a pivotal role in endothelial adhesion of monocytes via an increased expression of Mac-1. Cardiovasc Res. 2013;99:724-33 pubmed publisher
  25. Adamek A, Jung S, Dienesch C, Laser M, Ertl G, Bauersachs J, et al. Role of 5-lipoxygenase in myocardial ischemia-reperfusion injury in mice. Eur J Pharmacol. 2007;571:51-4 pubmed
    ..In summary, inhibition of 5-lipoxygenase does not affect cardiac ischemia-reperfusion injury but the post-ischemic inflammatory response. ..
  26. Chu J, Giannopoulos P, Ceballos Diaz C, Golde T, Pratico D. 5-Lipoxygenase gene transfer worsens memory, amyloid, and tau brain pathologies in a mouse model of Alzheimer disease. Ann Neurol. 2012;72:442-54 pubmed publisher
    The 5-lipoxygenase (5LO) enzyme is upregulated in Alzheimer disease (AD), and its genetic absence reduces A? levels in APP mice. However, its functional role in modulating tau neuropathology remains to be elucidated...
  27. Leedom A, Sullivan A, Dong B, Lau D, Gronert K. Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury. Am J Pathol. 2010;176:74-84 pubmed publisher
    ..In summary, our findings and the prominent expression of 15-LOX and ALX in epithelial cells and macrophages place the LXA(4) circuit as an endogenous regulator of pathological angiogenesis. ..
  28. Ballesteros I, Cuartero M, Pradillo J, de la Parra J, Pérez Ruiz A, Corbí A, et al. Rosiglitazone-induced CD36 up-regulation resolves inflammation by PPAR? and 5-LO-dependent pathways. J Leukoc Biol. 2014;95:587-98 pubmed publisher
    ..in experimental stroke has been explained by the inhibition of inflammatory genes, an action in which 5-LO, Alox5, is involved...
  29. Masid de Brito D, Queto T, Gaspar Elsas M, Xavier Elsas P. Roles of 5-lipoxygenase and cysteinyl-leukotriene type 1 receptors in the hematological response to allergen challenge and its prevention by diethylcarbamazine in a murine model of asthma. Mediators Inflamm. 2014;2014:403970 pubmed publisher
    ..Overall, 5-LO appears as indispensable to the systemic hematological response to allergen challenge, as well as to the effectiveness of DEC. ..
  30. Chen Y, Shan Y, Lu M, DeSouza N, Guo Z, Hoffman R, et al. Alox5 Blockade Eradicates JAK2V617F-Induced Polycythemia Vera in Mice. Cancer Res. 2017;77:164-174 pubmed publisher
    ..Our investigations focused on the lipid metabolic enzyme arachidonate 5-lipoxygenase (Alox5), which we found to be strongly upregulated by JAK2V617F in hematopoietic cells in vitro and in vivo Notably, ..
  31. Zhang Y, Hammarberg T, Radmark O, Samuelsson B, Ng C, Funk C, et al. Analysis of a nucleotide-binding site of 5-lipoxygenase by affinity labelling: binding characteristics and amino acid sequences. Biochem J. 2000;351 Pt 3:697-707 pubmed
    5-Lipoxygenase (5LO) catalyses the first two steps in the biosynthesis of leukotrienes, which are inflammatory mediators derived from arachidonic acid...
  32. Filgueiras L, Brandt S, Wang S, Wang Z, Morris D, Evans Molina C, et al. Leukotriene B4-mediated sterile inflammation promotes susceptibility to sepsis in a mouse model of type 1 diabetes. Sci Signal. 2015;8:ra10 pubmed publisher
    ..Expression of Alox5, which encodes 5-LO, and the concentration of the proinflammatory cytokine interleukin-1β (IL-1β) were also ..
  33. Poczobutt J, Nguyen T, Hanson D, Li H, Sippel T, Weiser Evans M, et al. Deletion of 5-Lipoxygenase in the Tumor Microenvironment Promotes Lung Cancer Progression and Metastasis through Regulating T Cell Recruitment. J Immunol. 2016;196:891-901 pubmed publisher
    ..These data reveal an antitumorigenic role for 5-LO products in the microenvironment during lung cancer progression through regulation of T cells and suggest that caution should be used in targeting this pathway in lung cancer. ..
  34. Singh A, Rahman T, Bartiss R, Arabshahi A, Prasain J, Barnes S, et al. Lipoxin A4, a 5-lipoxygenase pathway metabolite, modulates immune response during acute respiratory tularemia. J Leukoc Biol. 2017;101:531-542 pubmed publisher
    ..Tularemia pathogenesis was characterized in 5?lipoxygenase-deficient (Alox5-/-) mice that are incapable of generating LXA4 Increased release of proinflammatory ..
  35. Li J, Barrero C, Merali S, Pratico D. Genetic absence of ALOX5 protects from homocysteine-induced memory impairment, tau phosphorylation and synaptic pathology. Hum Mol Genet. 2017;26:1855-1862 pubmed publisher
    ..Because high Hcy is associated with an up-regulation of the ALOX5 gene product, the 5Lipoxygenase (5LO), herein we investigated whether this activation is responsible for the Hcy ..
  36. Rezende B, Athayde R, Gonçalves W, Resende C, Teles de Tolêdo Bernardes P, Perez D, et al. Inhibition of 5-lipoxygenase alleviates graft-versus-host disease. J Exp Med. 2017;214:3399-3415 pubmed publisher
    ..Our data provide evidence that the 5-LO/LTB4 axis orchestrates GVHD development and suggest it could be a target for the development of novel therapeutic strategies for GVHD treatment. ..
  37. Funk C, Cao R, Zhao L, Habenicht A. Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein E-deficient mice?. Ann N Y Acad Sci. 2006;1085:151-60 pubmed
    ..We are currently exploring the potential mechanisms for 5-LO/LT involvement in aneurysm pathogenesis and if this pathway might come into play in other models such as induction by angiotensin II. ..
  38. Qiu H, Gabrielsen A, Agardh H, Wan M, Wetterholm A, Wong C, et al. Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc Natl Acad Sci U S A. 2006;103:8161-6 pubmed
    ..The abundant expression of LTA4H and correlation with plaque instability identify LTA4H as a potential target for pharmacological intervention in treatment of human atherosclerosis. ..
  39. Lyons M. Arachidonate 5-lipoxygenase variants in atherosclerosis, obesity, and bone traits. Circ Res. 2006;98:e66 pubmed
  40. Poeckel D, Zemski Berry K, Murphy R, Funk C. Dual 12/15- and 5-lipoxygenase deficiency in macrophages alters arachidonic acid metabolism and attenuates peritonitis and atherosclerosis in ApoE knock-out mice. J Biol Chem. 2009;284:21077-89 pubmed publisher
    ..We propose that some of the inconsistent data obtained with single LO-deficient mice could be attributable to macrophage-specific patterns of altered AA metabolism. ..
  41. Blaho V, Zhang Y, Hughes Hanks J, Brown C. 5-Lipoxygenase-deficient mice infected with Borrelia burgdorferi develop persistent arthritis. J Immunol. 2011;186:3076-84 pubmed publisher
    ..These results demonstrate that products of the 5-LO metabolic pathway are not required for the development of disease in all models of arthritis and that caution should be used when targeting 5-LO as therapy for inflammatory diseases. ..
  42. Fredman G, Ozcan L, Spolitu S, Hellmann J, Spite M, Backs J, et al. Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway. Proc Natl Acad Sci U S A. 2014;111:14530-5 pubmed publisher
    ..Knowledge of this mechanism may provide new strategies for promoting inflammation resolution in chronic inflammatory diseases. ..
  43. Wu Y, Sun H, Song F, Huang C, Wang J. Deletion of Alox5 gene decreases osteogenic differentiation but increases adipogenic differentiation of mouse induced pluripotent stem cells. Cell Tissue Res. 2014;358:135-47 pubmed publisher
    ..b>Alox5 plays controversial and complex roles in the regulation of bone and fat metabolism...
  44. Wielockx B, Staelens J, Puimège L, Vanlaere I, Van Roy M, Van Lint P, et al. Description and mapping of the resistance of DBA/2 mice to TNF-induced lethal shock. J Immunol. 2007;178:5069-75 pubmed
    ..Definition of a critical region of 13 Mb on chromosome 6 was the highest mapping resolution obtained. Further analysis of candidate genes may provide a powerful tool to control TNF-induced pathologies in humans. ..
  45. Emerson M, Levine S. Experimental allergic encephalomyelitis is exacerbated in mice deficient for 12/15-lipoxygenase or 5-lipoxygenase. Brain Res. 2004;1021:140-5 pubmed
    ..Continued analysis will provide insight into the endogenous LO-generated effectors that assist in tempering EAE. ..
  46. Edmiston J, Lebman D. A transforming growth factor-beta regulable RNA-binding protein interacts specifically with germline Ig alpha transcripts. Int Immunol. 1997;9:427-33 pubmed
  47. 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. ..
  48. Cheng L, Sullivan B, Retana L, Allen C, Liang H, Locksley R. IgE-activated basophils regulate eosinophil tissue entry by modulating endothelial function. J Exp Med. 2015;212:513-24 pubmed publisher
    ..Thus, basophils are gatekeepers that link adaptive immunity with innate effector programs by altering access to tissue sites by activation-induced interactions with the endothelium. ..
  49. Segal B, Kuhns D, Ding L, Gallin J, Holland S. Thioglycollate peritonitis in mice lacking C5, 5-lipoxygenase, or p47(phox): complement, leukotrienes, and reactive oxidants in acute inflammation. J Leukoc Biol. 2002;71:410-6 pubmed
    ..5-Lipoxygenase-deficient (5LX(-/-)) and C5-deficient mice only generated about 50% as much peritoneal leukocytosis as wild-type mice following ..
  50. Monteiro A, Soledade E, Pinheiro C, Dellatorre Teixeira L, Oliveira G, Oliveira M, et al. Pivotal role of the 5-lipoxygenase pathway in lung injury after experimental sepsis. Am J Respir Cell Mol Biol. 2014;50:87-95 pubmed publisher
    ..These results point to an important role for 5-LO products in sepsis-induced lung injury and suggest that the use of 5-LO inhibitors may be of therapeutic benefit clinically. ..
  51. Walther M, Hofheinz K, Vogel R, Roffeis J, Kuhn H. The N-terminal ?-barrel domain of mammalian lipoxygenases including mouse 5-lipoxygenase is not essential for catalytic activity and membrane binding but exhibits regulatory functions. Arch Biochem Biophys. 2011;516:1-9 pubmed publisher
    ..Truncated enzyme species exhibit impaired membrane binding properties and altered reaction kinetics. Taken together, our data suggests a regulatory importance of the N-terminal ?-barrel domain for mammalian lipoxygenase isoforms. ..
  52. Chen Y, Sullivan C, Peng C, Shan Y, Hu Y, Li D, et al. A tumor suppressor function of the Msr1 gene in leukemia stem cells of chronic myeloid leukemia. Blood. 2011;118:390-400 pubmed publisher
    We have shown that Alox5 is a critical regulator of leukemia stem cells (LSCs) in a BCR-ABL-induced chronic myeloid leukemia (CML) mouse model, and we hypothesize that the Alox5 pathway represents a major molecular network that regulates ..
  53. Martel Pelletier J, Mineau F, Fahmi H, Laufer S, Reboul P, Boileau C, et al. Regulation of the expression of 5-lipoxygenase-activating protein/5-lipoxygenase and the synthesis of leukotriene B(4) in osteoarthritic chondrocytes: role of transforming growth factor beta and eicosanoids. Arthritis Rheum. 2004;50:3925-33 pubmed
    ..We also demonstrated that LTB(4) likely contributes to the up-regulation of important catabolic factors involved in the pathophysiology of OA, such as MMP. ..
  54. Coffey M, Phare S, Peters Golden M. Induction of inducible nitric oxide synthase by lipopolysaccharide/interferon gamma and sepsis down-regulates 5-lipoxygenase metabolism in murine alveolar macrophages. Exp Lung Res. 2004;30:615-33 pubmed
    ..iNOS knock-out mice were protected from the decrease in alveolar macrophage 5-lipoxygenase metabolism. iNOS regulates alveolar macrophage 5-lipoxygenase metabolism following endotoxin exposure. ..
  55. Rosen C, Ackert Bicknell C, Beamer W, Nelson T, Adamo M, Cohen P, et al. Allelic differences in a quantitative trait locus affecting insulin-like growth factor-I impact skeletal acquisition and body composition. Pediatr Nephrol. 2005;20:255-60 pubmed
    ..Lifelong changes in circulating and skeletal IGF-I may be relevant for the pathophysiology of several diseases, including chronic renal failure. ..
  56. Borges T, Alves É, Vasconcelos H, Carneiro F, Nicola A, Magalhaes K, et al. Differences in the modulation of reactive species, lipid bodies, cyclooxygenase-2, 5-lipoxygenase and PPAR-? in cerebral malaria-susceptible and resistant mice. Immunobiology. 2017;222:604-619 pubmed publisher
  57. Sapieha P, Stahl A, Chen J, Seaward M, Willett K, Krah N, et al. 5-Lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of ?-3 polyunsaturated fatty acids. Sci Transl Med. 2011;3:69ra12 pubmed publisher
    ..It also suggests that cyclooxygenase inhibitors such as aspirin and ibuprofen (but not lipoxygenase inhibitors such as zileuton) might be used without losing the beneficial effect of dietary ?-3 PUFA. ..
  58. Machado E, Ueta M, Lourenço E, Anibal F, Sorgi C, Soares E, et al. Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis. J Immunol. 2005;175:3892-9 pubmed
  59. Sezin T, Krajewski M, Wutkowski A, Mousavi S, Chakievska L, Bieber K, et al. The Leukotriene B4 and its Receptor BLT1 Act as Critical Drivers of Neutrophil Recruitment in Murine Bullous Pemphigoid-Like Epidermolysis Bullosa Acquisita. J Invest Dermatol. 2017;137:1104-1113 pubmed publisher
    ..Our results highlight LTB4/BLT1 as absolutely critical drivers of murine pemphigoid disease-like skin inflammation. ..
  60. Li J, Barrero C, Gupta S, Kruger W, Merali S, Pratico D. Homocysteine modulates 5-lipoxygenase expression level via DNA methylation. Aging Cell. 2017;16:273-280 pubmed publisher
    ..Alzheimer's disease is characterized by an upregulation of the 5-lipoxygenase (5LO), whose promoter is regulated by methylation...
  61. Liao T, Ke Y, Shao W, Haribabu B, Kaplan H, Sun D, et al. Blockade of the interaction of leukotriene b4 with its receptor prevents development of autoimmune uveitis. Invest Ophthalmol Vis Sci. 2006;47:1543-9 pubmed
    ..The results demonstrate a critical role for LTB4 in ocular inflammation and in the development and progression of EAU and suggest a new potential target for therapeutic intervention in this disease. ..
  62. Jiang X, Hawkins J, Lee J, Lizama C, Bos F, Zape J, et al. Let-7 microRNA-dependent control of leukotriene signaling regulates the transition of hematopoietic niche in mice. Nat Commun. 2017;8:128 pubmed publisher
    ..Here, the authors show that changing miRNA biogenesis and leukotriene B4 signaling in mice modulates this switch in the niche. ..
  63. Brogliato A, Moor A, Kesl S, Guilherme R, Georgii J, Peters Golden M, et al. Critical role of 5-lipoxygenase and heme oxygenase-1 in wound healing. J Invest Dermatol. 2014;134:1436-1445 pubmed publisher
    ..Taken together, our results show that 5-LO disruption improves wound healing and alters fibroblast function by an antioxidant mechanism based on HO-1 induction. Overexpression of HO-1 in wounds may facilitate early wound resolution. ..
  64. Ichinose F, Zapol W, Sapirstein A, Ullrich R, Tager A, Coggins K, et al. Attenuation of hypoxic pulmonary vasoconstriction by endotoxemia requires 5-lipoxygenase in mice. Circ Res. 2001;88:832-8 pubmed
    ..Taken together, these findings demonstrate that a 5-LO product, most likely a cysteinyl LT, contributes to the attenuation of HPV and to pulmonary injury after challenge with endotoxin. ..
  65. Santos P, Santos D, Ribeiro L, Fagundes C, de Paula T, Avila T, et al. The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis. PLoS Negl Trop Dis. 2013;7:e2390 pubmed publisher
    ..brasiliensis infection and identify relevant mechanisms for the control of fungal infection during the early stages of the host immune response. ..
  66. Collin M, Rossi A, Cuzzocrea S, Patel N, Di Paola R, Hadley J, et al. Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton. J Leukoc Biol. 2004;76:961-70 pubmed
  67. Giannopoulos P, Chu J, Joshi Y, Sperow M, Li J, Kirby L, et al. Gene knockout of 5-lipoxygenase rescues synaptic dysfunction and improves memory in the triple-transgenic model of Alzheimer's disease. Mol Psychiatry. 2014;19:511-8 pubmed publisher
    5-Lipoxygenase (5LO) is upregulated in Alzheimer's disease (AD) and in vivo modulates the amyloidotic phenotype of amyloid precursor protein transgenic mice...
  68. Chen M, Lam B, Luster A, Zarini S, Murphy R, Bair A, et al. Joint tissues amplify inflammation and alter their invasive behavior via leukotriene B4 in experimental inflammatory arthritis. J Immunol. 2010;185:5503-11 pubmed publisher
    ..Our results identify novel roles for FLSs and LTB(4) in joints, placing LTB(4) regulation of FLS biology at the center of a previously unrecognized amplification loop for synovial inflammation and tissue pathology. ..
  69. Nagashima T, Ichimiya S, Kikuchi T, Saito Y, Matsumiya H, Ara S, et al. Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by controlling primary B cells and their cognate T-cell help. Am J Pathol. 2011;178:222-32 pubmed publisher
    In this study, we report the unique role of arachidonate 5-lipoxygenase (Alox5) in the regulation of specific humoral immune responses...
  70. Karnam A, Holla S, Balaji K. Sonic hedgehog-responsive lipoxygenases and cyclooxygenase-2 modulate Dectin-1-induced inflammatory cytokines. Mol Immunol. 2015;68:280-9 pubmed publisher
    ..Together, the current study establishes Dectin-1-arbitrated host mediators that direct the differential regulation of immune responses during fungal infections and thus are potential candidates of therapeutic intervention. ..
  71. DiMeo D, Tian J, Zhang J, Narushima S, Berg D. Increased interleukin-10 production and Th2 skewing in the absence of 5-lipoxygenase. Immunology. 2008;123:250-62 pubmed
  72. Joshi V, Umashankara M, Ramakrishnan C, Nanjaraj Urs A, Suvilesh K, Velmurugan D, et al. Dimethyl ester of bilirubin exhibits anti-inflammatory activity through inhibition of secretory phospholipase A2, lipoxygenase and cyclooxygenase. Arch Biochem Biophys. 2016;598:28-39 pubmed publisher
    ..These data suggest that BD1 exhibits strong anti-inflammatory activity through inhibition of AA cascade enzymes which is of great therapeutic importance. ..
  73. Yan Y, Jiang W, Spinetti T, Tardivel A, Castillo R, Bourquin C, et al. Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity. 2013;38:1154-63 pubmed publisher
  74. Lemos H, Grespan R, Vieira S, Cunha T, Verri W, Fernandes K, et al. Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFNgamma production. Proc Natl Acad Sci U S A. 2009;106:5954-9 pubmed publisher
    ..We thus provide a mechanism for the pathogenic role of the IL-23/IL-17 axis in RA and also suggest an additional mechanism of action for nonsteroidal anti-inflammatory drugs. ..