The contributions of aspirin and microbial oxygenase to the biosynthesis of anti-inflammatory resolvins: novel oxygenase products from omega-3 polyunsaturated fatty acids.
Resolvins (Rvs) are oxygenated products derived from omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid that carry potent protective bioactions present in resolving inflammatory exudates. Resolvin E1 (RvE1) is biosynthesized in vivo from EPA via transcellular biosynthetic routes during cell-cell interactions, and thus RvE1 is formed in vivo during multicellular responses such as inflammation and microbial infections. RvE1 protects tissues from leukocyte-mediated injury and counterregulates proinflammatory gene expression. These newly identified Rvs may underlie the beneficial actions of omega-3 PUFAs especially in chronic disorders where unresolved inflammation is a key mechanism of pathogenesis. Here, we present an overview of the biosynthesis of RvE1, with a focus on the aspirin-triggered and microbial P450-initiated pathways. The generation of RvE1 and its actions appear to dampen acute leukocyte responses and facilitate the resolution of inflammation.
Arita
Makoto
M
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Clish
Clary B
CB
Serhan
Charles N
CN
D000818:Animals; D001241:Aspirin / Q000737:chemistry / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010105:Oxygenases / Q000737:chemistry / Q000502:physiology*
D015525:Fatty Acids, Omega-3; D015118:Eicosapentaenoic Acid; D010105:Oxygenases; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid; D001241:Aspirin