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- Title
Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids.
- Authors
Groeger, Alison L; Cipollina, Chiara; Cole, Marsha P; Woodcock, Steven R; Bonacci, Gustavo; Rudolph, Tanja K; Rudolph, Volker; Freeman, Bruce A; Schopfer, Francisco J
- Abstract
Electrophilic fatty acids are generated during inflammation by non-enzymatic reactions and can modulate inflammatory responses. We used a new mass spectrometry-based electrophile capture strategy to reveal the formation of electrophilic oxo-derivatives (EFOX) from the omega-3 fatty acids docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). These EFOX were generated by a cyclooxygenase-2 (COX-2)-catalyzed mechanism in activated macrophages. Modulation of COX-2 activity by aspirin increased the rate of EFOX production and their intracellular levels. Owing to their electrophilic nature, EFOX adducted to cysteine and histidine residues of proteins and activated Nrf2-dependent anti-oxidant gene expression. We confirmed the anti-inflammatory nature of DHA- and DPA-derived EFOX by showing that they can act as peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists and inhibit pro-inflammatory cytokine and nitric oxide production, all within biological concentration ranges. These data support the idea that EFOX are signaling mediators that transduce the beneficial clinical effects of omega-3 fatty acids, COX-2 and aspirin.
- Publication
Nature chemical biology, 2010, Vol 6, Issue 6, p433
- ISSN
1552-4469
- Publication type
Journal Article
- DOI
10.1038/nchembio.367