Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit
| العنوان: | Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit |
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| المؤلفون: | Caravaca, A. S., Gallina, A. L., Tarnawski, L., Shavva, V. S., Colas, R. A., Dalli, J., Malin, S. G., Hult, Henrik, 1975, Arnardottir, H., Olofsson, P. S. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America. 119(22) |
| مصطلحات موضوعية: | alpha7 Nicotinic Acetylcholine Receptor, Animals, Arachidonate 12-Lipoxygenase, Arachidonate 15-Lipoxygenase, Inflammation, Inflammation Mediators, Mice, Vagus Nerve, Vagus Nerve Stimulation, bungarotoxin receptor, cervonic acid, docosapentaenoic acid, zymosan, Alox15 protein, mouse, arachidonate 12 lipoxygenase, arachidonate 15 lipoxygenase, autacoid, a7nAChR gene, Alox15 gene, animal cell, animal experiment, animal model, animal tissue, Article, controlled study, disease duration, efferocytosis, ex vivo study, gene, in vivo study, lipidomics, male, nervous system inflammation, nonhuman, peritoneum exudate, peritonitis, surgical technique, animal, genetics, physiology, autonomic reflex, lipid mediators, neuroinflammation |
| الوصف: | Nonresolving inflammation underlies a range of chronic inflammatory diseases, and therapeutic acceleration of resolution of inflammation may improve outcomes. Neural reflexes regulate the intensity of inflammation (for example, through signals in the vagus nerve), but whether activation of the vagus nerve promotes the resolution of inflammation in vivo has been unknown. To investigate this, mice were subjected to electrical vagus nerve stimulation (VNS) or sham surgery at the cervical level followed by zymosan-induced peritonitis. The duration of inflammation resolution was significantly reduced and efferocytosis was significantly increased in mice treated with VNS as compared with sham. Lipid mediator (LM) metabololipidomics revealed that mice treated with VNS had higher levels of specialized proresolving mediators (SPMs), particularly from the omega-3 docosahexaenoic (DHA) and docosapentaenoic (n-3 DPA) metabolomes, in peritoneal exudates. VNS also shifted the ratio between proinflammatory and proresolving LMs toward a proresolving profile, but this effect by VNS was inverted in mice deficient in 12/15-lipoxgenase (Alox15), a key enzyme in this SPM biosynthesis. The significant VNS-mediated reduction of neutrophil numbers in peritoneal exudates was absent in mice deficient in the cholinergic α7-nicotinic acetylcholine receptor subunit (α7nAChR), an essential component of the inflammatory reflex. Thus, VNS increased local levels of SPM and accelerated resolution of inflammation in zymosan-induced peritonitis by a mechanism that involves Alox15 and requires the α7nAChR. |
| وصف الملف: | |
| الوصول الحر: | https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-324380Test https://doi.org/10.1073/pnas.2023285119Test |
| قاعدة البيانات: | SwePub |
| تدمد: | 00278424 10916490 |
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| DOI: | 10.1073/pnas.2023285119 |