Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008:3:279-312.
doi: 10.1146/annurev.pathmechdis.3.121806.151409.

Anti-inflammatory and proresolving lipid mediators

Charles N Serhan  1 , Stephanie Yacoubian, Rong Yang
Affiliations
Review

Anti-inflammatory and proresolving lipid mediators

Charles N Serhan et al. Annu Rev Pathol. 2008.

Abstract

The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that nonsteroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held as a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution and that possess potent anti-inflammatory and proresolving actions. A lipid-mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates, which also contain lipoxins and aspirin-triggered lipoxins generated from arachidonic acid. Given their potent bioactions, these new chemical mediator families were termed resolvins and protectins. Here, we review the recent advances in our understanding of the biosynthesis and stereospecific actions of these new proresolving mediators, which have also proven to be organ protective and antifibrotic.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Hypothetical scheme emphasizing the role of lipid mediators in orchestrating the resolution of acute inflammation.
Figure 2
Figure 2
Key eicosanoids that play pivotal roles in initiating inflammation and its resolution.
Figure 3
Figure 3
Biosynthesis of aspirin-triggered lipid mediators.
Figure 4
Figure 4
Biosynthesis of E-series resolvins.
Figure 5
Figure 5
Lipid mediator lipidomics: searches of databases and algorithms for identifying lipid mediators. Databases contain theoretical fragmentation post-mass spectrometry analysis. Known lipid mediators are matched according to fragments generated and their tandem MS-MS spectra stepwise to UV absorbance λ maxima and then to relative retention times. Databases were constructed using known lipid mediators, eicosanoids, prostaglandins, leukotrienes and lipoxins, as well as theoretical fragmentations expected for lipid mediators derived from other potential precursors.
Figure 6
Figure 6
Biosynthesis of D-series resolvins and protectins.
Figure 7
Figure 7
Biosynthesis of protectin D1/neuroprotectin D1 and related compounds.
Figure 8
Figure 8
General scheme for total organic synthesis of resolvins and protectins. Insets depict the characteristic UV spectrum associated with each of the key bioactive resolvins and protectins. The stereochemistry of endogenous RvE1, RvD1, and PD1 has been established, and the biological actions and physical properties of the endogenous compounds confirmed via total organic synthesis. In addition to the compounds shown, double bond isomers and chiral epimers have been synthesized to address the impact of stereochemistry and potency of the natural products. See text for details.
Figure 9
Figure 9
Resolvin E1 acts via ChemR23 and BLT1 peripheral blood leukocytes: Actions mediated via two distinct GPCRs. Agonist at ChemR23 and partial agonist/antagonist at BLT1.
Figure 10
Figure 10
Interactions between lipid mediators and peptide mediators during resolution: Resolvins enhance the scavenging and clearance of chemokines via macrophages.
Figure 11
Figure 11
Summation: Key points in summation.
See this image and copyright information in PMC

References

    1. Cotran RS, Kumar V, Collins T. Robbins Pathologic Basis of Disease. Philadelphia: W.B. Saunders Co; 1999. p. 1425.
    1. Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN. Lipid mediator class switching during acute inflammation: signals in resolution. Nature Immunol. 2001;2:612–19. This is the original report demonstrating temporal separation between individual classes of eicosanoids, i.e., dissociation between the formation and actions of prostaglandins, leukotrienes, and lipoxins in resolution. - PubMed
    1. Calder PC. Long-chain polyunsaturated fatty acids and inflammation. Scand J Food Nutr. 2006;50(S2):54–61.
    1. Serhan CN, Brain SD, Buckley CD, Gilroy DW, Haslett C, O’Neill LAJ, Perretti M, Rossi AG, Wallace JL. Resolution of inflammation: state of the art, definitions and terms. FASEB J. 2007;21:325–32. - PMC - PubMed
    1. Serhan CN, editor. Prostaglandins Leukot Essent Fatty Acids. 3–4. Vol. 73. 2005. Special Issue on Lipoxins and Aspirin-Triggered Lipoxins; pp. 139–321. This special issue features nineteen reviews by experts covering the anti-inflammatory actions of lipoxins, aspirin-triggered lipoxins, and therapeutic potential of stable metabolic analogs. This is a detailed resource for original research and critical review of results on lipoxins and their mechanism of action. - PubMed

Publication types

LinkOut - more resources