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http://purl.uniprot.org/citations/30197642http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30197642http://www.w3.org/2000/01/rdf-schema#comment"Arachidonate 15-lipoxygenase (ALOX15) and arachidonate 15-lipoxygenase, type B (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids and are upregulated in human alternatively activated macrophages (AAMs) induced by Th2 cytokine interleukin-4 (IL-4) and/or interleukin-13. Known primarily for roles in bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been implicated in various macrophage functions including efferocytosis and ferroptosis. Using a combination of inhibitors and siRNAs to suppress 15-LOX isoforms, we studied the role of 15-LOXs in cellular cholesterol homeostasis and immune function in naïve and AAMs. Silencing or inhibiting the 15-LOX isoforms impaired sterol regulatory element binding protein (SREBP)-2 signaling by inhibiting SREBP-2 processing into mature transcription factor and reduced SREBP-2 binding to sterol regulatory elements and subsequent target gene expression. Silencing ALOX15B reduced cellular cholesterol and the cholesterol intermediates desmosterol, lanosterol, 24,25-dihydrolanosterol, and lathosterol as well as oxysterols in IL-4-stimulated macrophages. In addition, attenuating both 15-LOX isoforms did not generally affect IL-4 gene expression but rather uniquely impacted IL-4-induced CCL17 production in an SREBP-2-dependent manner resulting in reduced T cell migration to macrophage conditioned media. In conclusion, we identified a novel role for ALOX15B, and to a lesser extent ALOX15, in cholesterol homeostasis and CCL17 production in human macrophages."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.org/dc/terms/identifier"doi:10.3389/fimmu.2018.01906"xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/author"Gupta S."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/author"Lutjohann D."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/author"Geisslinger G."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/author"Angioni C."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/author"Brune B."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/author"Namgaladze D."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/author"Snodgrass R.G."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/author"Zezina E."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/name"Front Immunol"xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/pages"1906"xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/title"A Novel Function for 15-Lipoxygenases in Cholesterol Homeostasis and CCL17 Production in Human Macrophages."xsd:string
http://purl.uniprot.org/citations/30197642http://purl.uniprot.org/core/volume"9"xsd:string
http://purl.uniprot.org/citations/30197642http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/30197642
http://purl.uniprot.org/citations/30197642http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/30197642
http://purl.uniprot.org/uniprot/#_B4DU98-mappedCitation-30197642http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30197642
http://purl.uniprot.org/uniprot/#_B4DNW8-mappedCitation-30197642http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30197642
http://purl.uniprot.org/uniprot/#_A8K9R4-mappedCitation-30197642http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30197642
http://purl.uniprot.org/uniprot/#_O15296-mappedCitation-30197642http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30197642
http://purl.uniprot.org/uniprot/O15296http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/30197642
http://purl.uniprot.org/uniprot/B4DNW8http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/30197642
http://purl.uniprot.org/uniprot/B4DU98http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/30197642