Biosynthesis of maresins

Stable Identifier
R-HSA-9018682
Type
Pathway
Species
Homo sapiens
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Maresins 1 and 2 (MaR1 and MaR2) are derived through the action of lipoxygenase 12 on the ω-3 fatty acid docosahexaenoic acid (DHA). MaRs are mainly produced by macrophages hence the derivation of the name from MAcrophage mediator RESolving INflammation. MaR1 exhibits potent anti-inflammatory, pro-resolving, analgesic and wound healing activities. Major cellular targets for the actions of MaR1 are vascular smooth muscle (VSM) cells and vascular endothelial cells. In these cells MaR1 attenuates the adhesion of monocytes to the endothelium induced by TNF-alpha. Maresin 1 also inhibits the production of reactive oxygen species by both VSM and endothelial cells. The major mechanism through which MaR1 exerts these effects is through down-regulation of the transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). MaR2 has been shown to reduce neutrophil infiltration and to enhance macrophage-mediated phagocytosis of dead and dying cells, a process termed efferocytosis. Two related structures, the maresin-like mediators (MaR-L1 and MaR-L2), are generated when the maresins produced by macrophages are released and acted upon by leukocytes and platelets (Hong et al. 2014). These, together with 14,21-dihydroxy-DHAs, rescue the reparative function of diabetes-impaired macrophages in diabetic wound healing (Hong et al. 2014, Tian et al. 2011, Boniakowski et al. 2017).

Literature References
PubMed ID Title Journal Year
26545300 Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance

Balas, L, Durand, T

Prog. Lipid Res. 2016
20708099 Specialized pro-resolving lipid mediators in the inflammatory response: An update

Bannenberg, G, Serhan, CN

Biochim. Biophys. Acta 2010
21839062 Autacoid 14S,21R-dihydroxy-docosahexaenoic acid counteracts diabetic impairment of macrophage prohealing functions

Tian, H, Lu, Y, Shah, SP, Hong, S

Am. J. Pathol. 2011
28630109 Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing

Boniakowski, AE, Kimball, AS, Jacobs, BN, Kunkel, SL, Gallagher, KA

J. Immunol. 2017
25200603 Maresin-like lipid mediators are produced by leukocytes and platelets and rescue reparative function of diabetes-impaired macrophages

Hong, S, Lu, Y, Tian, H, Alapure, BV, Wang, Q, Bunnell, BA, Laborde, JM

Chem. Biol. 2014
25139562 Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome

Serhan, CN, Dalli, J, Colas, RA, Winkler, JW, Chiang, N

Biochim. Biophys. Acta 2015
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