title: The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering.
abstract: Docosahexaenoic acid, a major omega-3 fatty acid in human brain, synapses, retina, and other neural tissues, displays beneficial actions in neuronal development, cancer, and inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatography-tandem mass spectrometry, that (10,17S)-docosatriene/neuroprotectin D1, now termed protectin D1 (PD1), is generated from docosahexaenoic acid by T helper type 2-skewed peripheral blood mononuclear cells in a lipoxygenase-dependent manner. PD1 blocked T cell migration in vivo, inhibited tumor necrosis factor alpha and interferon-gamma secretion, and promoted apoptosis mediated by raft clustering. These results demonstrated novel anti-inflammatory roles for PD1 in regulating events associated with inflammation and resolution.
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Amiram
authors.initials: A
authors.lastname: Ariel
authors.forename: Pin-Lan
authors.initials: PL
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wang-Xian
authors.initials: WX
authors.lastname: Tang
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Fredman
authors.forename: Song
authors.initials: S
authors.lastname: Hong
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Gotlinger
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid; D016207:Cytokines / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D021962:Membrane Microdomains / Q000737:chemistry*; D051379:Mice; D008956:Models, Chemical; D018384:Oxidative Stress; D010538:Peritonitis / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan / Q000737:chemistry
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; C487679:protectin D1; D004281:Docosahexaenoic Acids; D007371:Interferon-gamma; D015054:Zymosan; D001093:Arachidonate 15-Lipoxygenase