Cysteinyl leukotriene metabolism of human eosinophils in allergic disease |
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Affiliation: | 1. Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan;2. Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan;3. Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan;4. Department of Genome Research and Development, Kazusa DNA Research Institute, Chiba, Japan;5. Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan;6. Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan;7. Division of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Tokyo, Japan |
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Abstract: | Eosinophils are multifaceted immune cells with diverse functions that enhance allergic inflammation. Cysteinyl leukotrienes (cys-LTs), mainly synthesized in eosinophils, are a class of inflammatory lipid mediators produced via multiple enzymatic reactions from arachidonic acid. Multiple clinical studies have reported dysregulated fatty acid metabolism in severe asthma and aspirin-exacerbated respiratory diseases. Therefore, understanding the mechanism responsible for this metabolic abnormality has attracted a lot of attention. In eosinophils, various stimuli (including cytokines, chemokines, and pathogen-derived factors) prime and/or induce leukotriene generation and secretion. Cell–cell interactions with component cells (endothelial cells, epithelial cells, fibroblasts) also enhance this machinery to augment allergic responses. Nasal polyp-derived eosinophils from patients with eosinophilic rhinosinusitis present a characteristic fatty acid metabolism with selectively higher production of leukotriene D4. Interestingly, type 2 cytokines and microbiome components might be responsible for this metabolic change with altered enzyme expression. Here, we review the regulation of fatty acid metabolism, especially cys-LT metabolism, in human eosinophils toward allergic inflammatory status. |
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Keywords: | Asthma Aspirin-exacerbated respiratory disease Cysteinyl leukotrienes Eosinophils Eosinophilic rhinosinusitis AERD" },{" #name" :" keyword" ," $" :{" id" :" kwrd0040" }," $$" :[{" #name" :" text" ," _" :" aspirin-exacerbated respiratory diseases CCR3" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" C–C chemokine receptor type 3 Cys-LT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" cysteinyl leukotriene DPEP2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" dipeptidase-2 EOS" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" eosinophil FLAP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" 5-LOX-activating protein fMLP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" formyl-methionyl-leucyl-phenylalanine GGT5" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" gamma-glutamyl transferase-5 GM-CSF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" granulocyte-macrophage colony-stimulating factor HpETE" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" hydroperxy-eicosatetraenoic acid IFN" },{" #name" :" keyword" ," $" :{" id" :" kwrd0140" }," $$" :[{" #name" :" text" ," _" :" interferon IL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" interleukin LIR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0160" }," $$" :[{" #name" :" text" ," _" :" leukocyte Ig-like receptor LOX" },{" #name" :" keyword" ," $" :{" id" :" kwrd0170" }," $$" :[{" #name" :" text" ," _" :" lipoxygenase NOD2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0230" }," $$" :[{" #name" :" text" ," _" :" nucleotide binding oligomerization domain containing 2 PAF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0240" }," $$" :[{" #name" :" text" ," _" :" platelet activating factor PLA2" },{" #name" :" keyword" ," $" :{" id" :" kwrd0270" }," $$" :[{" #name" :" text" ," _" :" phospholipase A2 RANTES" },{" #name" :" keyword" ," $" :{" id" :" kwrd0280" }," $$" :[{" #name" :" text" ," _" :" regulated on activation, normal T cell expressed and secreted TNF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0290" }," $$" :[{" #name" :" text" ," _" :" tumor necrosis factor TLR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0300" }," $$" :[{" #name" :" text" ," _" :" toll-like receptor |
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