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Noradrenaline induces IL-1ra and IL-1 type II receptor expression in primary glial cells and protects against IL-1beta-induced neurotoxicity.

Authors: McNamee, EN  Ryan, KM  Kilroy, D  Connor, TJ 
Citation: McNamee EN, etal., Eur J Pharmacol. 2010 Jan 25;626(2-3):219-28. doi: 10.1016/j.ejphar.2009.09.054. Epub 2009 Oct 8.
Pubmed: (View Article at PubMed) PMID:19818755
DOI: Full-text: DOI:10.1016/j.ejphar.2009.09.054

The pro-inflammatory cytokine interleukin-1beta (IL-1beta) 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-1beta can be regulated by interleukin-1 receptor antagonist (IL-1ra), which prevents IL-1beta 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-1beta 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 beta-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-1beta 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.


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CRRD Object Information
CRRD ID: 8551853
Created: 2014-04-15
Species: All species
Last Modified: 2014-04-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.