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Plasticity of Leukocytic Exudates in Resolving Acute Inflammation Is Regulated by MicroRNA and Proresolving Mediators
Open accessAbstract
The magnitude and duration of acute inflammation are controlled by active resolution programs involving specialized proresolving mediators (SPMs; resolvins and maresins) and microRNAs (miRNAs). Here, we report that miR-466l was temporally regulated in murine exudate-infiltrating leukocytes. Neutrophil miR-466l overexpression in vivo promoted initiation of inflammation that anteceded macrophage expression of this miRNA, which accelerated resolution when overexpressed. In macrophages, miR-466l overexpression increased prostanoids and SPMs (e.g., resolvin D1 [RvD1] and RvD5), which enhanced resolution. RvD1, RvD2, maresin 1 (MaR1), and apoptotic neutrophils reduced miR-466l expression within human macrophages, a feedback regulation that most likely prepares for homeostasis. miR-466l was upregulated in peripheral blood of sepsis patients, and its increase correlated with nonsurvival from sepsis. SPMs and miR-466l regulated transcription factors activator protein 1 and nuclear factor κB1 in miRNA biogenesis. These results demonstrate pivotal roles for SPMs and miR-466l in dynamic leukocyte plasticity during resolution of acute inflammatory responses.
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“MiR-466l is upregulated in the peripheral blood of patients with sepsis, and its levels correlate with risk of death.”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [224]
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“During the inflammatory response, miR-466l is first overexpressed in neutrophils, acting proinflammatory, and then it is overexpressed in macrophages, leading to increase in prostanoids and specialized proresolving mediators (e.g., resolvin D1 [RvD1] and RvD5).”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [224]
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Metadata
- Authors
- Li, Y., Dalli, J., Chiang, N., Baron, R. M., Quintana, C., & Serhan, C. N.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Serhan, Charles N.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 39
- Issue
- 5
- Pages
- 885-898
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3888517
- OpenAlex
- W1971880637
- Cited by
- 126
- References
- 48
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 10 · 2020: 17 · 2019: 10 · 2018: 15 · 2017: 11 · 2016: 12 · 2015: 12 · 2014: 15 · 2013: 1
- FWCI
- 12.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL108801, R01HL112747)
- National Institute of General Medical Sciences (P01GM095467, R01GM038765)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- microRNA, specialized pro-resolving mediators, resolvin D1, resolvin D5, maresin 1, neutrophils, macrophages, prostanoids, apoptotic neutrophils, sepsis, activator protein-1, nuclear factor-kappaB, microRNA biogenesis
- MeSH terms
- Acute Disease, Animals, Chemotaxis, Docosahexaenoic Acids, Gene Expression Regulation, Humans, Macrophages, Male, Neutrophils, Peritonitis, Phagocytosis, Transcription, Genetic, Zymosan, NF-kappa B, Apoptosis, Sepsis, Transcription Factor AP-1, Inflammation Mediators, MicroRNAs, Mice
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