title: Interleukin-17A increases neurite outgrowth from adult postganglionic sympathetic neurons.
abstract: Inflammation can profoundly alter the structure and function of the nervous system. Interleukin (IL)-17 has been implicated in the pathogenesis of several inflammatory diseases associated with nervous system plasticity. However, the effects of IL-17 on the nervous system remain unexplored. Cell and explant culture techniques, immunohistochemistry, electrophysiology, and Ca2+ imaging were used to examine the impact of IL-17 on adult mouse sympathetic neurons. Receptors for IL-17 were present on postganglionic neurons from superior mesenteric ganglia (SMG). Supernatant from activated splenic T lymphocytes, which was abundant in IL-17, dramatically enhanced axonal length of SMG neurons. Importantly, IL-17-neutralizing antiserum abrogated the neurotrophic effect of splenocyte supernatant, and incubation of SMG neurons in IL-17 (1 ng/ml) significantly potentiated neurite outgrowth. The neurotrophic effect of IL-17 was accompanied by inhibition of voltage-dependent Ca2+ influx and was recapitulated by incubation of neurons in a blocker of N-type Ca2+ channels (ω-conotoxin GVIA; 30 nM). IL-17-induced neurite outgrowth in vitro appeared to be independent of glia, as treatment with a glial toxin (AraC; 5 μM) did not affect the outgrowth response to IL-17. Moreover, application of the cytokine to distal axons devoid of glial processes enhanced neurite extension. An inhibitor of the NF-κB pathway (SC-514; 20 μM) blocked the effects of IL-17. These data represent the first evidence that IL-17 can act on sympathetic somata and distal neurites to enhance neurite outgrowth, and identify a novel potential role for IL-17 in the neuroanatomical plasticity that accompanies inflammation.
authors.affiliation: Department of Biomedical and Molecular Sciences, Gastrointestinal Diseases Research Unit and Centre for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 2V7, Canada.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Chisholm
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cervi
authors.forename: Simrin
authors.initials: S
authors.lastname: Nagpal
authors.forename: Alan E
authors.initials: AE
authors.lastname: Lomax
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D020381:Interleukin-17 / Q000502:physiology*; D008297:Male; D051379:Mice; D016501:Neurites / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D053722:Receptors, Interleukin-17 / Q000819:agonists / Q000502:physiology; D017779:Sympathetic Fibers, Postganglionic / Q000502:physiology*
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17