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Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale.

Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale.
Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale.
The n-6 fatty acid arachidonic acid (AA; 20:4n-6) gives rise to eicosanoid mediators that have established roles in inflammation and AA metabolism is a long recognised target for commonly used anti-inflammatory therapies. It has generally been assumed that all AA-derived eicosanoids are pro-inflammatory. However this is an over-simplification since some actions of eicosanoids are anti-inflammatory (e.g. prostaglandin (PG) E2 inhibits production of some inflammatory cytokines) and it has been discovered quite recently that PGE2 inhibits production of inflammatory leukotrienes and induces production of inflammation resolving lipoxin A4. The n-3 fatty acids from oily fish and “fish oils”, eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), are incorporated into inflammatory cell phospholipids in a time- and dose-dependent manner. They are incorporated partly at the expense of AA, but also of other n-6 fatty acids. EPA and DHA inhibit AA metabolism. Thus production of AA-derived eicosanoids is decreased by these n-3 fatty acids; this occurs in a dose-dependent manner. EPA gives rise to an alternative family of eicosanoids (e.g. PGE3), which frequently, but not always, have lower potency than those produced from AA. Recently a new family of EPA- and DHA-derived lipid mediators called resolvins (E- and D-series) has been described. These have potent anti-inflammatory and inflammation resolving properties in model systems. It seems likely that these mediators will explain many of the anti-inflammatory actions of n-3 fatty acids that have been described. In addition to modifying the profile of lipid-derived mediators, fatty acids can also influence peptide mediator (i.e. cytokine) production. To a certain extent this action may be due to the altered profile of regulatory eicosanoids, but it seems likely that eicosanoid-independent actions are a more important mechanism. Indeed effects on transcription factors that regulate inflammatory gene expression (e.g. nuclear factor ?B) seem to be important.
cytokine, eicosanoid, fatty acid, fish oil, inflammation
0300-9084
791-795
Calder, P.C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Calder, P.C.
1797e54f-378e-4dcb-80a4-3e30018f07a6

Calder, P.C. (2009) Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochimie, 91 (6), 791-795. (doi:10.1016/j.biochi.2009.01.008).

Record type: Article

Abstract

The n-6 fatty acid arachidonic acid (AA; 20:4n-6) gives rise to eicosanoid mediators that have established roles in inflammation and AA metabolism is a long recognised target for commonly used anti-inflammatory therapies. It has generally been assumed that all AA-derived eicosanoids are pro-inflammatory. However this is an over-simplification since some actions of eicosanoids are anti-inflammatory (e.g. prostaglandin (PG) E2 inhibits production of some inflammatory cytokines) and it has been discovered quite recently that PGE2 inhibits production of inflammatory leukotrienes and induces production of inflammation resolving lipoxin A4. The n-3 fatty acids from oily fish and “fish oils”, eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), are incorporated into inflammatory cell phospholipids in a time- and dose-dependent manner. They are incorporated partly at the expense of AA, but also of other n-6 fatty acids. EPA and DHA inhibit AA metabolism. Thus production of AA-derived eicosanoids is decreased by these n-3 fatty acids; this occurs in a dose-dependent manner. EPA gives rise to an alternative family of eicosanoids (e.g. PGE3), which frequently, but not always, have lower potency than those produced from AA. Recently a new family of EPA- and DHA-derived lipid mediators called resolvins (E- and D-series) has been described. These have potent anti-inflammatory and inflammation resolving properties in model systems. It seems likely that these mediators will explain many of the anti-inflammatory actions of n-3 fatty acids that have been described. In addition to modifying the profile of lipid-derived mediators, fatty acids can also influence peptide mediator (i.e. cytokine) production. To a certain extent this action may be due to the altered profile of regulatory eicosanoids, but it seems likely that eicosanoid-independent actions are a more important mechanism. Indeed effects on transcription factors that regulate inflammatory gene expression (e.g. nuclear factor ?B) seem to be important.

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More information

Published date: June 2009
Keywords: cytokine, eicosanoid, fatty acid, fish oil, inflammation

Identifiers

Local EPrints ID: 147697
URI: https://eprints.soton.ac.uk/id/eprint/147697
ISSN: 0300-9084
PURE UUID: 4bd148df-851a-47e6-89aa-605ccfc094d7

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Date deposited: 26 Apr 2010 12:03
Last modified: 18 Jul 2017 19:33

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