5-Oxo-ETE and Inflammation

  • William S. PowellEmail author
  • Joshua Rokach
Part of the Progress in Inflammation Research book series (PIR)


5-Oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) is a potent proinflammatory 5-lipoxygenase product. It is formed by oxidation of 5S-HETE by the highly selective dehydrogenase 5-HEDH, which is expressed in both inflammatory and structural cells. Its synthesis is regulated by the availability of the obligate cofactor NADP+ and is favored by conditions such as oxidative stress and activation of the respiratory burst in phagocytic cells. The actions of 5-oxo-ETE are mediated by the Gi-coupled OXE receptor that is found in many species but not in rodents. This receptor is highly expressed on eosinophils and basophils, and is also found on neutrophils, monocytes/macrophages, and various cancer cell lines. Because of its potent actions on eosinophils 5-oxo-ETE may be an important proinflammatory mediator in asthma and other eosinophilic diseases. 5-Oxo-ETE may also be involved in cancer, as it promotes the survival and proliferation of a number of cancer cell lines and rescues these cells from apoptosis induced by inhibitors of the 5-LO pathway. OXE receptor antagonists, which are currently under development, may be useful therapeutic agents in asthma and other eosinophilic disorders and possibly also in cancer.


5-HETE 5-HODE 5-Hydroxyeicosanoid dehydrogenase 5-Lipoxygenase 5-Oxo-ETE 5-Oxo-ODE Antagonists Asthma Basophils Cancer Chemoattractants Eosinophils G protein-coupled receptors Glutathione GM-CSF Inflammation Mead acid Monocytes NADP+ Neutrophils OXE receptor OXER1 Oxidative stress PC3 prostate tumor cells Platelets Polyunsaturated fatty acids Respiratory burst Sebaleic acid Structure-activity relationships Transcellular biosynthesis 



12S-Hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid


5-Hydroxyeicosanoid dehydrogenase




5-Oxo,12S-hydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid


5-Oxo,15S-hydroxy-6E,8Z,11Z,13E-eicosatetraenoic acid


5-Oxo-20-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid


5-Oxo-6E,8Z,11Z,14Z,17Z -eicosapentaenoic acid


5-Oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid


5-Oxo-6E,8Z,11Z-eicosatrienoic acid


5-Oxo-6E,8Z-octadecadienoic acid


5S,12S-Dihydroxy-6E,8Z,10E,14Z-eicosatetraenoic acid


5S-Hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid


5S-Hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid




5S-Hydroxy-6E,8Z-octadecadienoic acid


5S-Hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid


Arachidonic acid


Diacyl glycerol


5Z,8Z,11Z,14Z,17Z-Eicosapentaenoic acid


5-Lipoxygenase activating protein


5-Oxo-7-glutathionyl-8,11,14-eicosatrienoic acid


Granulocyte-macrophage colony stimulating factor


Hydroxyl-carboxylic acid receptor



MAP kinases

Mitogen-activated protein kinases


Matrix metalloproteinase-9


Platelet-activating factor


Phosphoinositide 3-kinase


Protein kinase C


Phospholipase C


Polyunsaturated fatty acid


Tumor necrosis factor-α


Urokinase-type plasminogen activator receptor



Work done in the authors’ laboratories was supported by grants from the Canadian Institutes of Health Research (WSP, MOP-6254 and PPP-99490), the Quebec Heart and Stroke Foundation (WSP), the American Asthma Foundation (JR, 12–0049), and the National Heart, Lung, and Blood Institute (JR, R01HL081873). The Meakins-Christie Laboratories-MUHC-RI are supported in part by a Center grant from Le Fond de la Recherche en Santé du Québec as well as by the JT Costello Memorial Research Fund. JR also wishes to acknowledge the National Science Foundation for the AMX-360 (grant no. CHE-90-13145) and Bruker 400 MHz (grant no. CHE-03-42251) NMR instruments. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Meakins-Christie LaboratoriesMcGill University Health Centre Research Institute, Centre for Translational BiologyMontrealCanada
  2. 2.Department of ChemistryClaude Pepper Institute, Florida Institute of TechnologyMelbourneUSA

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