Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 626, Issue 2-3, Pages 219-228Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2009.09.054
Keywords
IL-1 beta; IL-1ra; IL-1RII; Noradrenaline; beta-adrenoceptor; Neuroprotection; Glial cell
Categories
Funding
- Science Foundation Ireland
- Health Research Board
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The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) 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-1 beta can be regulated by interleukin-1 receptor antagonist (IL-1 ra), which prevents IL-1 beta from acting on the IL-1 type 1 receptor (IL-1RI). Another negative regulator of the IL-1 system is the IL-1 type If 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-1 ra and IL-1RII from primary rat mixed glial cells. In contrast noradrenaline did not alter IL-1 beta expression, or expression of IL-1RI or the IL-1 type 1 receptor accessory protein (IL-1 RAcp); 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-1 beta 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. (C) 2009 Elsevier B.V. All rights reserved.
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