Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit

• 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. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

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

mouse

nervous system inflammation

nonhuman

peritoneum exudate

peritonitis

surgical technique

animal

genetics

physiology

autonomic reflex

lipid mediators

neuroinflammation

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)