MURAL - Maynooth University Research Archive Library



    Noradrenaline acting at β-adrenoceptors induces expression of IL-1β and its negative regulators IL-1ra and IL-1RII, and drives an overall anti-inflammatory phenotype in rat cortex


    McNamee, Eóin N. and Griffin, Éadaoin W. and Ryan, Karen M. and Ryan, Katie J. and Heffernan, Sheena and Harkin, Andrew and Connor, Thomas J. (2010) Noradrenaline acting at β-adrenoceptors induces expression of IL-1β and its negative regulators IL-1ra and IL-1RII, and drives an overall anti-inflammatory phenotype in rat cortex. Neuropharmacology, 59. pp. 37-48. ISSN 1873-7064

    [img]
    Preview
    Download (475kB) | Preview


    Share your research

    Twitter Facebook LinkedIn GooglePlus Email more...



    Add this article to your Mendeley library


    Abstract

    Evidence indicates that noradrenaline elicits anti-inflammatory actions in the central nervous system (CNS), and plays a neuroprotective role where inflammatory events contribute to pathology. Here we examined the ability of pharmacological enhancement of central noradrenergic tone to impact upon activation of the IL-1 system in rat brain. Treatment with the noradrenaline reuptake inhibitor reboxetine combined with the α2-adrenoceptor antagonist idazoxan induced expression of IL-1β as well as its negative regulators, IL-1 receptor antagonist (IL-1ra) and IL-1 type II receptor (IL-1RII) in rat cortex. The ability of reboxetine/idazoxan treatment to activate the IL-1 system was mediated by β-adrenoceptors, as the aforementioned effects were blocked by the β-adrenoceptor antagonist propranolol. Moreover, administration of the brain penetrant β2-adrenoceptor agonist clenbuterol induced expression of IL-1β, IL-1ra and IL-1RII in rat brain. This action was selective to the IL-1 system, as other inflammatory cytokines including TNF-α, IL-6 or IFN-γ were not induced by clenbuterol. Induction of IL-1β was accompanied by activation of NFκB and of the MAP kinase ERK, and clenbuterol also induced expression of the IL-1β-inducible gene CINC-1. The ability of clenbuterol to activate the IL-1 system was blocked by propranolol, and was mimicked by the highly selective β2-adrenoceptor agonist formoterol. Despite the ability of clenbuterol to activate the central IL-1 system, it largely combated the neuroinflammatory response induced by systemic inflammatory stimulus (bacterial lipopolysaccharide; LPS). Specifically, whilst the ability of clenbuterol to induce expression of IL-1RII and IL-1Ra was maintained following the inflammatory challenge, its ability to induce IL-1β was reduced. In addition, clenbuterol suppressed LPS-induced expression of the inflammatory cytokines TNF-α and IL-6, the inflammatory chemokines RANTES and IP-10, the co-stimulatory molecules CD40 and ICAM-1. Thus overall, clenbuterol suppresses the innate inflammatory response in rat brain.

    Item Type: Article
    Keywords: Noradrenaline; β-adrenoceptors; IL-1; IL-1ra; IL-1RII; Neuroinflammation; LPS;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 12601
    Identification Number: https://doi.org/10.1016/j.neuropharm.2010.03.014
    Depositing User: Eoin McNamee
    Date Deposited: 24 Mar 2020 12:45
    Journal or Publication Title: Neuropharmacology
    Publisher: Elsevier
    Refereed: Yes
    URI:

    Repository Staff Only(login required)

    View Item Item control page

    Downloads

    Downloads per month over past year