Ryan, Katie J. and Griffin, Éadaoin and Yssel, Justin D. and Ryan, Karen M. and McNamee, Eóin N. and Harkin, Andrew and Connor, Thomas J.
(2013)
Stimulation of central β2-adrenoceptors suppresses NFκB activity in rat brain: a role for IκB.
Neurochemistry International, 63 (5).
ISSN 1872-9754
Abstract
In this study we examined the impact of systemic treatment with the long-acting brain penetrant β2-adrenoceptor agonist clenbuterol on NFκB activity and IκB expression in rat brain. Clenbuterol decreased NFκB activity (p65 DNA binding) in nuclear extracts prepared from rat cortex and hippocampus for up to 8h following a single treatment. This was accompanied by increased expression of IκBα mRNA and protein. The temporal increase in IκB protein expression paralleled the suppression of NFκB activity, suggesting that IκBα mediates the suppression NFκB activity observed. These actions of clenbuterol were prevented by pre-treatment with the non-selective β-adrenoceptor antagonist propranolol, the β2-adrenoceptor antagonist ICI-118,551, but not the β1-adrenoceptor antagonist metoprolol, suggesting that the effects of clenbuterol on IκBα expression and NFκB activity are mediated specifically by the β2-adrenoceptor. In addition, the actions of clenbuterol were mimicked by systemic administration of another highly selective long-acting β2-adrenoceptor agonist formoterol. As neurodegenerative diseases are associated with inflammation we determined if clenbuterol could suppress NFκB activation that occurs in response to an inflammatory stimulus. In this regard we demonstrate that clenbuterol inhibited IκB phosphorylation and IκB degradation and inhibited NFκB activity in hippocampus and cortex of rats following a central injection of the inflammagen bacterial lipopolysaccharide (LPS). In tandem, clenbuterol blocked expression of the NFκB-inducible genes TNF-α and ICAM-1 following LPS administration. Our finding that clenbuterol and formoterol inhibit NFκB activity in the CNS further supports the idea that β2-adrenoceptors may be an attractive target for treating neuroinflammation and combating inflammation-related neurodegeneration.
| Item Type: |
Article
|
| Keywords: |
β2-adrenoceptor;
Clenbuterol;
Formoterol;
NFκB;
IκBα;
Neuroinflammation;
LPS;
Brain; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
12589 |
| Identification Number: |
https://doi.org/10.1016/j.neuint.2013.07.006 |
| Depositing User: |
Eoin McNamee
|
| Date Deposited: |
23 Mar 2020 12:18 |
| Journal or Publication Title: |
Neurochemistry International |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| 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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