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Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids

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Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids. / Groeger, Alison L; Cipollina, Chiara; Cole, Marsha P; Woodcock, Steven R; Bonacci, Gustavo; Rudolph, Tanja K; Rudolph, Volker; Freeman, Bruce A; Schopfer, Francisco J.

In: NAT CHEM BIOL, Vol. 6, No. 6, 06.2010, p. 433-441.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Groeger, AL, Cipollina, C, Cole, MP, Woodcock, SR, Bonacci, G, Rudolph, TK, Rudolph, V, Freeman, BA & Schopfer, FJ 2010, 'Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids', NAT CHEM BIOL, vol. 6, no. 6, pp. 433-441. https://doi.org/10.1038/nchembio.367

APA

Groeger, A. L., Cipollina, C., Cole, M. P., Woodcock, S. R., Bonacci, G., Rudolph, T. K., Rudolph, V., Freeman, B. A., & Schopfer, F. J. (2010). Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids. NAT CHEM BIOL, 6(6), 433-441. https://doi.org/10.1038/nchembio.367

Vancouver

Groeger AL, Cipollina C, Cole MP, Woodcock SR, Bonacci G, Rudolph TK et al. Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids. NAT CHEM BIOL. 2010 Jun;6(6):433-441. https://doi.org/10.1038/nchembio.367

Bibtex

@article{517cd3142b47494885ae42eabb51ecd6,
title = "Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids",
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.",
keywords = "Anti-Inflammatory Agents/chemical synthesis, Borohydrides/pharmacology, Cell Line, Cell Membrane/metabolism, Cyclooxygenase 2/metabolism, Docosahexaenoic Acids/chemistry, Fatty Acids, Omega-3/metabolism, Fatty Acids, Unsaturated/metabolism, Glutathione/metabolism, Humans, Hydroxylation, Interleukin-10/genetics, Interleukin-6/genetics, Macrophages/drug effects, PPAR gamma/metabolism",
author = "Groeger, {Alison L} and Chiara Cipollina and Cole, {Marsha P} and Woodcock, {Steven R} and Gustavo Bonacci and Rudolph, {Tanja K} and Volker Rudolph and Freeman, {Bruce A} and Schopfer, {Francisco J}",
year = "2010",
month = jun,
doi = "10.1038/nchembio.367",
language = "English",
volume = "6",
pages = "433--441",
journal = "NAT CHEM BIOL",
issn = "1552-4450",
publisher = "NATURE PUBLISHING GROUP",
number = "6",

}

RIS

TY - JOUR

T1 - Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids

AU - Groeger, Alison L

AU - Cipollina, Chiara

AU - Cole, Marsha P

AU - Woodcock, Steven R

AU - Bonacci, Gustavo

AU - Rudolph, Tanja K

AU - Rudolph, Volker

AU - Freeman, Bruce A

AU - Schopfer, Francisco J

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

KW - Anti-Inflammatory Agents/chemical synthesis

KW - Borohydrides/pharmacology

KW - Cell Line

KW - Cell Membrane/metabolism

KW - Cyclooxygenase 2/metabolism

KW - Docosahexaenoic Acids/chemistry

KW - Fatty Acids, Omega-3/metabolism

KW - Fatty Acids, Unsaturated/metabolism

KW - Glutathione/metabolism

KW - Humans

KW - Hydroxylation

KW - Interleukin-10/genetics

KW - Interleukin-6/genetics

KW - Macrophages/drug effects

KW - PPAR gamma/metabolism

U2 - 10.1038/nchembio.367

DO - 10.1038/nchembio.367

M3 - SCORING: Journal article

C2 - 20436486

VL - 6

SP - 433

EP - 441

JO - NAT CHEM BIOL

JF - NAT CHEM BIOL

SN - 1552-4450

IS - 6

ER -