Noradrenaline acting at central ?-adrenoceptors induces interleukin-10 and suppressor of cytokine signaling-3 expression in rat brain: Implications for neurodegeneration

Evidence indicates that the monoamine neurotransmitter noradrenaline elicits anti-inflammatory actions in the central nervous system (CNS), and consequently may play a neuroprotective role where inflammatory events contribute to CNS pathology. Here we examined the ability of pharmacologically enhancing central noradrenergic tone to induce expression of anti-inflammatory cytokines in rat brain. Administration of the noradrenaline reuptake inhibitor reboxetine (15 mg/kg; ip) combined with the ?2-adrenoceptor antagonist idazoxan (1 mg/kg; ip) induced interleukin-10 (IL-10) expression in rat cortex and hippocampus. In addition, these drug treatments induced IL-10 signaling as indicated by increased STAT3 phosphorylation and suppressor of cytokine signaling-3 (SOCS-3) mRNA expression. In contrast to the profound increase in IL-10 induced by the reboxetine/idazoxan combination, the other two broad spectrum anti-inflammatory cytokines IL-4 and TGF-? were not induced by this treatment. The ability of combined treatment with reboxetine and idazoxan to induce IL-10 and SOCS3 expression was mediated by ?-adrenoceptor activation, as their induction was blocked by pre-treatment with the ?-adrenoceptor antagonist propranolol. Moreover, administration of the brain penetrant ?2-adrenoceptor agonist clenbuterol induced a time- and dose-dependent increase in central IL-10 and SOCS3 expression, and the ability of clenbuterol to induce IL-10 and SOCS-3 expression was blocked by the centrally acting ?-adrenoceptor antagonist, propranolol, and was mimicked by the highly selective ?2-adrenoceptor agonist formoterol. In all, these data indicate that increasing central noradrenergic tone induces IL-10 production and signaling in the CNS, which may protect against neurodegeneration.

• Fecha de publicación: 2010
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/25919
• Acceso en línea: https://doi.org/10.1016/j.bbi.2010.02.005; https://repository.urosario.edu.co/handle/10336/25919
• Palabra clave: IL-10; SOCS3; Noradrenaline; ?-Adrenoceptor; STAT3; Brain; Anti-inflammatory
• License: Restringido (Acceso a grupos específicos)