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Protectin DX, a Double Lipoxygenase Product of DHA, Inhibits Both ROS Production in Human Neutrophils and Cyclooxygenase Activities
Author(s) -
Liu Miao,
Boussetta Tarek,
MakniMaalej Karama,
Fay Michèle,
Driss Fathi,
ElBenna Jamel,
Lagarde Michel,
Guichardant Michel
Publication year - 2014
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-013-3863-6
Subject(s) - leukotriene b4 , nadph oxidase , chemistry , myeloperoxidase , arachidonate 5 lipoxygenase , reactive oxygen species , leukotriene , cyclooxygenase , inflammation , biochemistry , chemotaxis , pharmacology , enzyme , arachidonic acid , immunology , biology , receptor , asthma
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 B 4 (LTB 4 ). Taken together, our results suggest that PDX could be a protective agent against neutrophil invasion in chronic inflammatory diseases.