The DOI matches its Crossref record; 32 of the 33 references it cites were found in a registry or an index.
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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Cites
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738
Resolution of inflammation: the beginning programs the end
Serhan, C. N., & Savill, J. (2005) · Nature Immunology · doi:10.1038/ni1276 · Cited by 2,552
Self-citationThe many roles of chemokines and chemokine receptors in inflammation
Charo, I. F., & Ransohoff, R. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmra052723 · Cited by 2,523
Serhan, C. N., Hong, S., Gronert, K., Colgan, S. P., Devchand, P. R., Mirick, G., & Moussignac, R.-L. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020760 · Cited by 1,650
Lipid mediator class switching during acute inflammation: signals in resolution
Levy, B. D., Clish, C. B., Schmidt, B., Gronert, K., & Serhan, C. N. (2001) · Nature Immunology · doi:10.1038/89759 · Cited by 1,453
Self-citationAnti-Inflammatory Therapy in Chronic Disease: Challenges and Opportunities
Tabas, I., & Glass, C. K. (2013) · Science · doi:10.1126/science.1230720 · Cited by 1,093
Serhan, C. N. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141647 · Cited by 1,020
Resolvins and protectins in inflammation resolution
Serhan, C. N., & Petasis, N. A. (2011) · Chemical Reviews · doi:10.1021/cr100396c · Cited by 996
Self-citationResolvin D1 binds human phagocytes with evidence for proresolving receptors
Krishnamoorthy, S., Recchiuti, A., Chiang, N., Yacoubian, S., Lee, C., Yang, R., Petasis, N. A., & Serhan, C. N. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907342107 · Cited by 752
Molecular Circuits of Resolution: Formation and Actions of Resolvins and Protectins
Bannenberg, G. L., Chiang, N., Ariel, A., Arita, M., Tjonahen, E., Gotlinger, K. H., Hong, S., & Serhan, C. N. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.7.4345 · Cited by 699
The axonal chemoattractant netrin-1 is also a chemorepellent for trochlear motor axons
Colamarino, S. A., & Tessier‐Lavigne, M. (1995) · Cell · doi:10.1016/0092-8674(95)90083-7 · Cited by 582
Dalli, J., & Serhan, C. N. (2012) · Blood · doi:10.1182/blood-2012-04-423525 · Cited by 572
Anti-Inflammatory and Proresolving Lipid Mediators
Serhan, C. N., Yacoubian, S., & Yang, R. (2008) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.151409 · Cited by 528
Merched, A. J., Ko, K., Gotlinger, K. H., Serhan, C. N., & Chan, L. (2008) · The FASEB Journal · doi:10.1096/fj.08-112201 · Cited by 414
Self-citationHypoxia-inducible factor–dependent induction of netrin-1 dampens inflammation caused by hypoxia
Rosenberger, P., Schwab, J. M., Mirakaj, V., Masekowsky, E., Mager, A., Morote–Garcia, J. C., Unertl, K. E., & Eltzschig, H. K. (2009) · Nature Immunology · doi:10.1038/ni.1683 · Cited by 406
The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors
Wu, J. Y., Feng, L., Park, H.-T., Havlioglu, N., Wen, L., Tang, H., Bacon, K. B., Jiang, Z., Zhang, X.-C., & Rao, Y. (2001) · Nature · doi:10.1038/35073616 · Cited by 397
Rethinking inflammation: neural circuits in the regulation of immunity
Olofsson, P. S., Rosas‐Ballina, M., Levine, Y. A., & Tracey, K. J. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01138.x · Cited by 393
van Gils, J. M., Derby, M. C., Fernandes, L. R., Ramkhelawon, B., Ray, T. D., Rayner, K. J., Parathath, S., Distel, E., Feig, J. L., Alvarez-Leite, J. I., et al. (2012) · Nature Immunology · doi:10.1038/ni.2205 · Cited by 365
Leukocyte-Endothelial Cell Interactions in the Inflammatory Response
Müller, W. A. (2002) · Laboratory Investigation · doi:10.1038/labinvest.3780446 · Cited by 303
Netrin-1 inhibits leukocyte migration in vitro and in vivo
Ly, N. P., Komatsuzaki, K., Fraser, I. P., Tseng, A. A., Prodhan, P., Moore, K. J., & Kinane, T. B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506233102 · Cited by 267
Resolvin D1 Limits Polymorphonuclear Leukocyte Recruitment to Inflammatory Loci
Norling, L. V., Dalli, J., Flower, R. J., Serhan, C. N., & Perretti, M. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.249508 · Cited by 260
Rapid Appearance of Resolvin Precursors in Inflammatory Exudates: Novel Mechanisms in Resolution
Kasuga, K., Yang, R., Porter, T. F., Agrawal, N., Petasis, N. A., Irimia, D., Toner, M., & Serhan, C. N. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.12.8677 · Cited by 241
The resolution of inflammation: the devil in the flask and in the details
Serhan, C. N. (2011) · The FASEB Journal · doi:10.1096/fj.11-0502ufm · Cited by 195
Role of Basic Science in the Development of New Medicines: Examples from the Eicosanoid Field
Samuelsson, B. O. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.x112.351437 · Cited by 157
Netrin-1 Dampens Pulmonary Inflammation during Acute Lung Injury
Mirakaj, V., Thix, C. A., Laucher, S., Mielke, C., Morote–Garcia, J. C., Schmit, M. A., Henes, J., Unertl, K. E., Köhler, D., & Rosenberger, P. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200905-0717oc · Cited by 138
Aherne, C. M., Collins, C. B., Masterson, J. C., Tizzano, M., Boyle, T. A., Westrich, J. A., Parnes, J. A., Furuta, G. T., Rivera–Nieves, J., & Eltzschig, H. K. (2011) · Gut · doi:10.1136/gutjnl-2011-300012 · Cited by 129
Asfaha, S., MacNaughton, W. K., Appleyard, C. B., Chadee, K., & Wallace, J. L. (2001) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2001.281.3.g635 · Cited by 83
Netrin-1 Signaling Dampens Inflammatory Peritonitis
Mirakaj, V., Gatidou, D., Pötzsch, C., König, K., & Rosenberger, P. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002671 · Cited by 83
(2012) · Europe PMC (PubMed Central) · Cited by 75
Repulsive guidance molecule-A (RGM-A) inhibits leukocyte migration and mitigates inflammation
Mirakaj, V., Brown, S., Laucher, S., Steinl, C., Klein, G., Köhler, D., Skutella, T., Meisel, C., Brommer, B., Rosenberger, P., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015605108 · Cited by 61
Neuronal migration and molecular conservation with leukocyte chemotaxisPreprint
Rao, Y., Wong, K., Ward, M. E., Jürgensen, C., & Wu, J. Y. (2002) · Genes & Development · doi:10.1101/gad.1005802 · Cited by 35
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Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities
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Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators
Serhan, C. N., & Levy, B. D. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97943 · Cited by 1,344
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Soehnlein, O., & Libby, P. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00198-1 · Cited by 1,085
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Chavan, S. S., Pavlov, V. A., & Tracey, K. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.008 · Cited by 678
Resolution of Inflammation: What Controls Its Onset?
Sugimoto, M. A., Sousa, L. P., Pinho, V., Perretti, M., & Teixeira, M. M. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00160 · Cited by 638
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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