Controlling inflammation: a fat chance?

Roderick J Flower, Mauro Perretti, Roderick J Flower, Mauro Perretti

Abstract

The inflammatory response protects the body against infection and injury but can itself become deregulated with deleterious consequences to the host. It is now clear that several endogenous biochemical pathways activated during defense reactions can counterregulate inflammation. New experimental evidence adds resolvin E1 to this group of endogenous inhibitors and provides further rationale for the beneficial effects of dietary supplementation with fish oils. It also highlights an unexpected twist in the pharmacology of aspirin.

Figures

Figure 1.
Figure 1.
Resolvin E1 and its receptor; a novel antiinflammatory circuit. Transcellular synthesis of resolvin E1 from diet-ingested eicosapentaenoic acid (EPA) occurs within the microcirculation by the concerted action of endothelial cell COX-2 and neutrophil 5-lipoxygenase (5-LO). After aspirin treatment, resolvin E1 synthesis occurs even in the absence of inflammation. Aspirin inactivates COX-2 but permits continuing generation of the intermediate 18R-hydroxy-EPA which is converted to resolvin E1 (or 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid) by the 5′ lipoxygenase in adjacent neutrophils. This lipid can then act in a paracrine or autocrine fashion on a specific seven-transmembrane G protein–coupled receptor, termed ChemR23, to bring about inhibitory effects on leukocyte activation presumably with reduced synthesis and reduced release of proinflammatory mediators: the end point of resolvin E1–ChemR23 mediated effects is a reduced flux of blood-borne cells into the site of inflammation.

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Source: PubMed

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