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Vagus nerve controls resolution and pro-resolving mediators of inflammation
Open accessAbstract
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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“Inflammation is associated with autonomic dysfunction (Black, 2003; McGovern and Mazzone, 2014; Mirakaj et al., 2014), so this result is compatible with the hypothesis that the reduction in hs-CRP may be due in part to improved autonomic function.”
From Effectiveness of a Novel Qigong Meditative Movement Practice for Impaired Health in Flight Attendants Exposed to Second-Hand Cigarette Smoke (2017) · cites this paper as Mirakaj et al., 2014
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Metadata
- 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
- Publisher
- Rockefeller University Press
- Published
- 2014-05-26
- Volume
- 211
- Issue
- 6
- Pages
- 1037-1048
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4042652
- 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
- bronze
- doi.org
- 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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