McNamee, Eóin N. and Ryan, Karen M. and Kilroy, Dana and Connor, Thomas J. (2010) Noradrenaline induces IL-1ra and IL-1 type II receptor expression in primary glial cells and protects against IL-1β-induced neurotoxicity. European Journal of Pharmacology, 626. pp. 219-228. ISSN 0014-2999

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Abstract

The pro-inflammatory cytokine interleukin-1β (IL-1β) plays a key role in initiating an immune response within the central nervous system (CNS), and is thought to be a significant contributor to the neurodegenerative process. The actions of IL-1β can be regulated by interleukin-1 receptor antagonist (IL-1ra), which prevents IL-1β from acting on the IL-1 type I receptor (IL-1RI). Another negative regulator of the IL-1 system is the IL-1 type II receptor (IL-1RII); a decoy receptor that serves to sequester IL-1. Consequently, pharmacological strategies that tip the balance in favour of IL-1ra and IL-1RII may be of therapeutic benefit. Evidence suggests that the neurotransmitter noradrenaline elicits anti-inflammatory actions in the CNS, and consequently may play an endogenous neuroprotective role. Here we report that noradrenaline induces production of IL-1ra and IL-1RII from primary rat mixed glial cells. In contrast, noradrenaline did not alter IL-1β expression, or expression of IL-1RI or the IL-1 type I receptor accessory protein (IL-1RAcp); both of which are required for IL-1 signalling. Our results demonstrate that the ability of noradrenaline to induce IL-1ra and IL-1RII is mediated via β-adrenoceptor activation and downstream activation of protein kinase A and extracellular signal-regulated kinase (ERK). In parallel with its ability to increase IL-1ra and IL-1RII, noradrenaline prevented neurotoxicity in cortical primary neurons induced by conditioned medium from IL-1β treated mixed glial cells. These data indicate that noradrenaline negatively regulates IL-1 system in glial cells and has neuroprotective properties in situations where IL-1 contributes to pathology.

Item Type:	Article
Keywords:	IL-1β; IL-1ra; IL-1RII; Noradrenaline; β-adrenoceptor; Neuroprotection; Glial cell;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12602
Identification Number:	https://doi.org/10.1016/j.ejphar.2009.09.054
Depositing User:	Eoin McNamee
Date Deposited:	24 Mar 2020 12:46
Journal or Publication Title:	European Journal of Pharmacology
Publisher:	Elsevier
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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