Identification and Actions of the Maresin 1 Metabolome in Infectious Inflammation

Colas, Romain A.; Dalli, Jesmond; Chiang, Nan; Vlasakov, Iliyan; Sanger, Julia M.; Riley, Ian R.; Serhan, Charles N.

doi:10.4049/jimmunol.1600837

Cited by 68 publications

(56 citation statements)

References 35 publications

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“…Also, both MaR-1 and its metabolite 22-OH-MaR-1 act at the human leukotriene-1 receptor and affect LTB 4 signaling. These results recognize heretofore unidentified molecules and establish unique functions for the macrophagederived MaR-1 bioactive metabolome (102,104).…”

Section: Macrophages and Mars Nexusmentioning

confidence: 59%

Unified nexus of macrophages and maresins in cardiac reparative mechanisms

Jadapalli

Halade

2018

FASEB j.

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Macrophages are immune-sensing "big eater" phagocytic cells responsible for an innate, adaptive, and regenerative response. After myocardial infarction, macrophages predominantly clear the deceased cardiomyocyte apoptotic or necrotic neutrophils to develop a regenerative and reparative program with the activation of the lipoxygenase-mediated maresin (MaR) metabolome at the site of ischemic injury. The specialized proresolving molecule and macrophage mediator in resolving inflammation, MaR-1, produced by human macrophages, has potent defining effects that limit polymorphonuclear neutrophil infiltration, enhance uptake of apoptotic PMNs, regulate inflammation resolution and tissue regeneration, and reduce pain. In addition to proresolving and anti-inflammatory actions, MaR-1 displays potent tissue regenerative effects in stroke and is an antinociceptive. Macrophages actively participate in the biosynthesis of bioactive MaR-2, which exhibits anti-inflammatory, proresolving, and atherosclerotic effects. A new class of macrophage-derived molecules, MaR conjugates in tissue regeneration, is identified that regulates phagocytosis and the repair and regeneration of damaged tissue. The presented review provides a current summary of the effect of MaR in resolution pathophysiology, with relevance to a cardiac repair program.-Jadapalli, J. K., Halade, G. V. Unified nexus of macrophages and maresins in cardiac reparative mechanisms.

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Section: Macrophages and Mars Nexusmentioning

confidence: 59%

Unified nexus of macrophages and maresins in cardiac reparative mechanisms

Jadapalli

Halade

2018

FASEB j.

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“…Macrophages convert this mediator to 14‐oxo‐MaR1, which displays blunted biological actions in comparison to the parent mediator. Neutrophils convert MaR1 to 22‐OH‐MaR1 that retains the potent biological actions of the parent SPM, including its ability to regulate the activation of the LTB 4 receptor (BLT 1 receptor ) by its cognate ligand (Colas et al ., ). In the CNS, MaR1 also displays reparative actions, where MaR1 (1 μg per mouse, i.v.)…”

Section: The Identification and Structure Elucidation Of Novel Immunomentioning

confidence: 97%

“…Some SPM also act as antagonists to receptors of pro‐inflammatory eicosanoids. RvE1, MaR1 and its further metabolite 22‐OH‐MaR1 are all competitive antagonists of BLT1 receptors (Figure ) inhibiting the signalling and biological actions of the potent leukocyte chemoattractant LTB 4 (Arita et al ., ; El Kebir et al ., ; Oh et al ., ; Colas et al ., ). In human neutrophils, BLT1 antagonism enhances neutrophil apoptosis (El Kebir et al ., ).…”

Section: How Do the Spm Exert Their Biological Actions?mentioning

confidence: 97%

Identification and structure elucidation of the pro‐resolving mediators provides novel leads for resolution pharmacology

Dalli

Serhan

2018

British J Pharmacology

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111

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Inflammatory diseases are a major socio‐economic burden, with the incidence of such conditions on the rise, especially in western societies. For decades, the primary treatment paradigm for many of these conditions was to develop drugs that inhibit or antagonize the production and biological actions of molecules that were thought to be the culprits in propagating disease; these include cytokines and eicosanoids. This approach is effective in controlling disease propagation; however, long‐term exposure to these anti‐inflammatories is also associated with many side effects, some of which are severe, including immune‐suppression. The discovery that termination of self‐limited acute inflammation is an active process orchestrated by endogenous mediators, including the essential fatty acid‐derived resolvins, protectins and maresins, has provided novel opportunities for the design of therapeutics that control inflammation with a lower burden of side effects. This is because at variance to anti‐inflammatories, pro‐resolving mediators do not completely inhibit inflammatory responses; instead, these mediators reprogramme the immune response to accelerate the termination of inflammation, facilitating the regain of function. The scope of this review is to highlight the biological actions of these autacoids and their potential utility as lead compounds in developing resolution pharmacology‐based therapeutics. Linked Articles This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc

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“…Of note, in some instances, SPMs display receptor-level antagonism at pro-phlogistic receptors. This antagonism is exemplified by RvE1 and MaR1 inhibition of leukotriene B 4 interactions with its cognate receptor BLT1 [87,88]. ALX/FPR2 receptors are broadly expressed in human tissues that were once thought to be expressed only on leucocytes (Fig.…”

Section: Quantitative Definitions For Resolution Physiology-pharmacolmentioning

confidence: 99%

Novel mediators and mechanisms in the resolution of infectious inflammation: evidence for vagus regulation

2019

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Excessive chronic inflammation is linked to many diseases and considered a stress factor in humans (Robbins Pathologic Basis of Disease. Philadelphia: W.B. Saunders Co., 1999, Proc Natl Acad Sci USA, 2008, 105: 17949, Immunity, 44, 2016, 44: 463, N Engl J Med, 2011, 364: 656). Today, the resolution of inflammation is widely recognized as a cellular biochemically active process involving biosynthesis of a novel superfamily of endogenous chemical signals coined specialized pro‐resolving mediators (SPMs; Nature, 2014, 510:92). Herein, we review recent evidence, indicating a role for the vagus nerve and vagotomy in the regulation of lipid mediators. Vagotomy reduces pro‐resolving mediators, including the lipoxins, resolvins, protectins and maresins, delaying resolution in mouse peritonitis. Vagotomy also delays resolution of Escherichia coli infection in mice. Specifically, right vagus regulates peritoneal Group 3 innate lymphoid cell (ILC‐3) number and peritoneal macrophage responses with lipid mediator profile signatures with elevated pro‐inflammatory eicosanoids and reduced resolvins, including the novel protective immunoresolvent agonist protectin conjugate in tissue regeneration1 (PCTR1). Acetylcholine upregulates PCTR biosynthesis, and administration of PCTR1 to vagotomized mice restores tissue resolution and host responses to E. coli infections. Results obtained with human vagus ex vivo indicate that vagus can produce both pro‐inflammatory eicosanoids, such as prostaglandins and leukotrienes, as well as the SPM. Electrical stimulation of human vagus in vitro reduces both prostaglandins and leukotrienes and enhances resolvins and the other SPM. These results elucidate a host protective mechanism mediated by vagus stimulation of SPM that includes resolvins and PCTR1 to regulate myeloid antimicrobial functions and resolution of infection. Moreover, they define a new pro‐resolution of inflammation reflex operative in mice and human tissue that involves a vagus SPM circuit.

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Identification and Actions of the Maresin 1 Metabolome in Infectious Inflammation

Cited by 68 publications

References 35 publications

Unified nexus of macrophages and maresins in cardiac reparative mechanisms

Unified nexus of macrophages and maresins in cardiac reparative mechanisms

Identification and structure elucidation of the pro‐resolving mediators provides novel leads for resolution pharmacology

Novel mediators and mechanisms in the resolution of infectious inflammation: evidence for vagus regulation

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