Inhibition of microglial inflammatory responses by norepinephrine: effects on nitric oxide and interleukin-1β production

摘要: Background: Under pathological conditions, microglia produce proinflammatory mediators which contribute to neurologic damage, and whose levels can be modulated by endogenous factors including neurotransmitters such as norepinephrine (NE). We investigated the ability of NE suppress microglial activation, in particular its effects on induction activity inducible form nitric oxide synthase (NOS2) possible role that IL-1β plays response. Methods: Rat cortical were stimulated with bacterial lipopolysaccharide (LPS) induce NOS2 expression (assessed nitrite nitrate accumulation, NO production, mRNA levels) release ELISA). Effects examined co-incubating cells different concentrations NE, adrenergic receptor agonists antagonists, cAMP analogs, protein kinase (PK) A adenylate cyclase (AC) inhibitors. NFκB:IκB pathway using selective a NFκB inhibitor measuring IκBα western blots. for was tested examining caspase-1 inhibitors deficient cells. Results: LPS caused time-dependent increase production; blocked inhibitor. dose-dependently reduced generation, via activation β2-adrenergic receptors (β2-ARs), loss inhibitory IkBα protein. replicated dibutyryl-cyclic AMP. However, co-incubation either PKA or AC did not reverse suppressive but instead production. suggested since potently incubation inhibitor, levels, had no effect IL-receptor antagonist biphasic inhibited production microglia. Conclusions: reduces however does play critical nor mediating effects. Changes magnitude kinetics may modulate well suppression NE. These results suggest dysregulation central cathecolaminergic system detrimental inflammatory responses brain damage neurological disease trauma.