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Functional interleukin-6 receptor- is located in tanycytes at the base of the third ventricle

Journal article
Authors Fredrik Anesten
Cristiano Santos
Edwin Gidestrand
Erik Schéle
Vilborg Palsdottir
Teodor Swedung-Wettervik
B. Meister
Karolina P Skibicka
John-Olov Jansson
Published in Journal of Neuroendocrinology
Volume 29
Issue 12
ISSN 0953-8194
Publication year 2017
Published at Institute of Neuroscience and Physiology, Department of Physiology
Language en
Links doi.org/10.1111/jne.12546
Keywords hypothalamus, IL-6, IL-6R, tanycytes, third ventricle, hypothalamic tanycytes, mediobasal hypothalamus, arcuate nucleus, energy-balance, body-weight, il-6, obesity, brain, mice, amylin, Endocrinology & Metabolism, Neurosciences & Neurology
Subject categories Physiology

Abstract

Interleukin (IL)-6(-)/(-) mice develop mature onset obesity, whereas i.c.v. injection of IL-6 decreases obesity in rodents. Moreover, levels of IL-6 in cerebrospinal fluid (CSF) were reported to be inversely correlated with obesity in humans. Tanycytes lining the base of the third ventricle (3V) in the hypothalamus have recently been reported to be of importance for metabolism. In the present study, we investigated whether tanycytes could respond to IL-6 in the CSF. With immunohistochemistry using a well characterised antibody directed against the ligand binding receptor for IL-6, IL-6 receptor (IL-6R), it was found that tanycytes, identified by the two markers, vimentin and dopamine- and cAMP-regulated phosphoprotein of 32 kDa, contained IL-6R. There were fewer IL-6R on another type of ventricle-lining cells, ependymal cells, as identified by the marker glucose transporter-1. To demonstrate that the immunoreactive IL-6R were responsive to IL-6, we injected IL-6 i.c.v. This treatment increased immunoreactive phosphorylated signal transducer and activator of transcription-3 (pSTAT3) in tanycytes after 5minutes and in cells in the medial part of the arcuate nucleus after 5 and 15 minutes. Intracerebroventricular injection of leptin exerted similar effects. As expected, i.p. injection of leptin also induced pSTAT3 staining in the hypothalamus, whereas i.p. IL-6 injection had little effect on this parameter. Intracerebroventricular or i.p. injection of vehicle only had no effect on pSTAT3-immunoreactivity. In summary, there are functional IL-6R on tanycytes at the bottom of the 3V, in agreement with the possibility that ventricular administration of IL-6 decreases obesity in mice via an effect on this cell type.

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