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Remodelling of the sympathetic nervous system following peripheral inflammation
Author(s) -
Lomax Alan,
Chisholm Susan,
Nagpal Simrin,
Cervi Andrea
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.304.4
Subject(s) - neurite , myenteric plexus , sympathetic nervous system , pathogenesis , inflammation , interstitial cell of cajal , medicine , electrophysiology , enteric nervous system , neuroscience , inflammatory bowel disease , endocrinology , immunohistochemistry , biology , in vitro , disease , blood pressure , biochemistry
Remodelling of the sympathetic innervation of the colon occurs during inflammatory bowel disease (IBD). However, the mechanisms are unclear. We hypothesized that interleukin (IL)‐17A, a key cytokine in IBD pathogenesis, plays a role in this remodelling. Chronic DSS‐induced colitis in mice and immunohistochemistry were used to study sympathetic neuroplasticity. Sympathetic neurite outgrowth was examined from superior mesenteric ganglia (SMG) neurons cultured in the presence of IL‐17A. Electrophysiology and Ca 2+ imaging techniques were also used. Colitis enhanced sympathetic innervation of the colonic myenteric plexus and mucosa. Glial inhibition and explant studies suggest that IL‐17A acts directly on axons to promote SMG outgrowth. Incubation of SMG neurons in IL‐17A reduced voltage‐gated Ca 2+ current (I Ca ) and depolarisation‐induced Ca 2+ influx in growth cones. This effect was abrogated by an inhibitor of NF‐κB signalling which also prevented IL‐17A‐induced neurite outgrowth. Blockade of I Ca with a VGC channel blocker reproduced the effects of IL‐17A on axonal outgrowth. Therefore, IL‐17A may contribute to sympathetic remodelling during IBD through activation of NF‐κB and inhibition of Ca 2+ influx.