title: Protectin DX, a double lipoxygenase product of DHA, inhibits both ROS production in human neutrophils and cyclooxygenase activities.
abstract: Neutrophils play a major role in inflammation by releasing large amounts of reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and myeloperoxidase (MPO). This ROS overproduction is mediated by phosphorylation of the NOX subunits in an uncontrolled manner. Therefore, targeting neutrophil subunits would represent a promising strategy to moderate NOX activity, lower ROS, and other inflammatory agents, such as cytokines and leukotrienes, produced by neutrophils. For this purpose, we investigated the effects of protectin DX (PDX)-a docosahexaenoic acid di-hydroxylated product which inhibits blood platelet aggregation-on neutrophil activation in vitro. We found that PDX decreases ROS production, inhibits NOX activation and MPO release from neutrophils. We also confirm, that PDX is an anti-aggregatory and anti-inflammatory agent by inhibiting both cyclooxygenase-1 and -2 (COX-1 and COX-2, E.C. 1.14.99.1) as well as COX-2 in lipopolysaccharides-treated human neutrophils. However, PDX has no effect on the 5-lipoxygenase pathway that produces the chemotactic agent leukotriene B4 (LTB4). Taken together, our results suggest that PDX could be a protective agent against neutrophil invasion in chronic inflammatory diseases.
authors.affiliation: UMR 1060 Inserm (CarMeN), IMBL/INSA-Lyon, Université de Lyon, 69621, Villeurbanne, France.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.forename: Tarek
authors.initials: T
authors.lastname: Boussetta
authors.forename: Karama
authors.initials: K
authors.lastname: Makni-Maalej
authors.forename: Michèle
authors.initials: M
authors.lastname: Fay
authors.forename: Fathi
authors.initials: F
authors.lastname: Driss
authors.forename: Jamel
authors.initials: J
authors.lastname: El-Benna
authors.forename: Michel
authors.initials: M
authors.lastname: Lagarde
authors.forename: Michel
authors.initials: M
authors.lastname: Guichardant
mesh_terms: D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D007536:Isomerism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D011453:Prostaglandins; D017382:Reactive Oxygen Species; C487679:protectin D1; D013481:Superoxides; D004281:Docosahexaenoic Acids; D012694:Serine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D008084:Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D013755:Tetradecanoylphorbol Acetate