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Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome
Open accessAbstract
Acute inflammatory responses are protective, yet without timely resolution can lead to chronic inflammation and organ fibrosis. A systems approach to investigate self-limited (self-resolving) inflammatory exudates in mice and structural elucidation uncovered novel resolution phase mediators in vivo that stimulate endogenous resolution mechanisms in inflammation. Resolving inflammatory exudates and human leukocytes utilize DHA and other n-3 EFA to produce three structurally distinct families of potent di- and trihydroxy-containing products, with several stereospecific potent mediators in each family. Given their potent and stereoselective picogram actions, specific members of these new families of mediators from the DHA metabolome were named D-series resolvins (Resolvin D1 to Resolvin D6), protectins (including protectin D1-neuroprotectin D1), and maresins (MaR1 and MaR2). In this review, we focus on a) biosynthesis of protectins and maresins as anti-inflammatory-pro-resolving mediators; b) their complete stereochemical assignments and actions in vivo in disease models. Each pathway involves the biosynthesis of epoxide-containing intermediates produced from hydroperoxy-containing precursors from human leukocytes and within exudates. Also, aspirin triggers an endogenous DHA metabolome that biosynthesizes potent products in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1)]. Identification and structural elucidation of these new families of bioactive mediators in resolution has opened the possibility of diverse patho-physiologic actions in several processes including infection, inflammatory pain, tissue regeneration, neuroprotection-neurodegenerative disorders, wound healing, and others. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".
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“NPD1 is highlighted here as a neuroprotective mediator in ischemic stroke, as defined by cellular and molecular targets, and demonstrated that the pathway that leads to its formation was enhanced in its neuroprotective bioactivity by the presence of aspirin (Marcheselli et al., 2003) by aspirin-triggered NPD1 (Bazan et al., 2012; Serhan et al., 2015; Serhan and Petasis, 2011).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Serhan et al., 2015
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“NPD1 is highlighted here as a neuroprotective mediator in ischemic stroke, as defined by cellular and molecular targets, and demonstrated that the pathway that leads to its formation was enhanced in its neuroprotective bioactivity by the presence of aspirin (Marcheselli et al., 2003) by aspirin-triggered NPD1 (Bazan et al., 2012; Serhan et al., 2015; Serhan and Petasis, 2011).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Serhan et al., 2015
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Metadata
- Authors
- Serhan, C. N., Dalli, J., Colas, R. A., Winkler, J. W., & Chiang, N.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Serhan, Charles N.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 1851
- Issue
- 4
- Pages
- 397-413
- ISSN
- 1388-1981 (ISSN-L)
- PMC
- PMC4324013
- OpenAlex
- W2049424212
- Cited by
- 492
- References
- 166
- Citations by year
- 2026: 19 · 2025: 32 · 2024: 35 · 2023: 38 · 2022: 52 · 2021: 56 · 2020: 55 · 2019: 34 · 2018: 57 · 2017: 52 · 2016: 32 · 2015: 28
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mérieux Foundation (R01GM038765)
- NIH (P01GM095467)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- protectins, maresins, resolvins, neuroprotectin D1, protectin D1, omega-3 fatty acids, acute inflammation, inflammation resolution, epoxide intermediate, hydroperoxides, leukocytes, aspirin, neuroprotection, wound healing, inflammatory pain
- MeSH terms
- Animals, Anti-Inflammatory Agents, Aspirin, Docosahexaenoic Acids, Humans, Inflammation, Structure-Activity Relationship, Molecular Structure, Signal Transduction, Metabolome, Lipoxygenases
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