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Plasticity of Leukocytic Exudates in Resolving Acute Inflammation Is Regulated by MicroRNA and Proresolving Mediators
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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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