Reactome | Biosynthesis of maresins

Biosynthesis of maresins

Stable Identifier

R-HSA-9018682

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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
20708099	Specialized pro-resolving lipid mediators in the inflammatory response: An update Bannenberg, G, Serhan, CN	Biochim. Biophys. Acta	2010
26545300	Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance Balas, L, Durand, T	Prog. Lipid Res.	2016
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