Cited by 176Vagus Nerve Stimulation ResearchFatty Acid Research and HealthPhagocytosis and Immune Regulation

Vagus nerve controls resolution and pro-resolving mediators of inflammation

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Mirakaj, Valbona, Dalli, Jesmond, Granja, Tiago, Rosenberger, Peter, Serhan, Charles N.·2014·Journal of Experimental Medicine

Abstract

Resolution of inflammation is now recognized as a biosynthetically active process involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal inflammation that the vagus nerve regulates local expression of netrin-1, an axonal guidance molecule that activates resolution, and that vagotomy reduced local pro-resolving mediators, thereby delaying resolution. In netrin-1(+/-) mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1(+/+). Netrin-1 shortened the resolution interval, decreasing exudate neutrophils, reducing proinflammatory mediators, and stimulating the production of resolvins, protectins, and lipoxins. Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins. Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other's expression and enhanced efferocytosis. These results indicate that the vagus nerve regulates both netrin-1 and pro-resolving lipid mediators, which act in a bidirectional fashion to stimulate resolution, and provide evidence for a novel mechanism for local neuronal control of resolution.

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Authors
Mirakaj, V., Dalli, J., Granja, T., Rosenberger, P., & Serhan, C. N.
Affiliations
  • Brigham and Women's Hospital (US)
  • University of Tübingen (DE)
Corresponding author
  • Rosenberger, Peter
  • Serhan, Charles N.
Venue
Journal of Experimental Medicine
Published
2014-05-26
Volume
211
Issue
6
Pages
1037-1048
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2162294258
Cited by
176
References
33
Citations by year
2026: 6 · 2025: 13 · 2024: 8 · 2023: 6 · 2022: 20 · 2021: 27 · 2020: 14 · 2019: 9 · 2018: 19 · 2017: 21 · 2016: 15 · 2015: 12 · 2014: 5
FWCI
9.20
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Institute of General Medical Sciences (R01GM038765)
  • National Institute of Neurological Disorders and Stroke (R01NS067686)
Topics
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
vagus nerve, inflammation resolution, specialized pro-resolving mediators, netrin-1, resolvin D1, vagotomy, peritonitis, zymosan, neutrophil influx, efferocytosis, resolvins, protectins, lipoxins, monocytes, bidirectional signaling
MeSH terms
Netrin-1, Animals, Cells, Cultured, Chemotaxis, Docosahexaenoic Acids, Humans, Inflammation, Lipids, Macrophages, Mice, Inbred C57BL, Microscopy, Fluorescence, Monocytes, Nerve Growth Factors, Neutrophils, Peritonitis, Recombinant Proteins, Vagotomy, Vagus Nerve, Zymosan, Blotting, Western, Mice, Knockout, Inflammation Mediators, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Lipoxins, Mice

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