Anti-inflammatory effects of noradrenaline on LPS-treated microglial cells: Suppression of NFκB nuclear translocation and subsequent STAT1 phosphorylation.

摘要: Noradrenaline (NA) has marked anti-inflammatory effects on activated microglial cells. The present study was conducted to elucidate the mechanisms underlying NA using rat primary cultured NA, an α1 agonist, phenylephrine (Phe) and a β2 terbutaline (Ter) suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) release by microglia prevented neuronal degeneration in LPS-treated neuron-microglia coculture. agents expression of mRNA encoding proinflammatory mediators. Both α1-selective blocker terazocine β2-selective butoxamine overcame suppressive NA. cAMP-dependent kinase (PKA) inhibitors did not abolish effects. LPS decreased IκB leading NFκB translocation into nuclei, then induced phosphorylation signal transducer activator transcription 1 (STAT1) interferon regulatory factor (IRF1). inhibited LPS-induced these changes. When knocked down with siRNA, STAT1 IRF1 abolished. suppress IL-6 expression. These results suggest that one critical is inhibition translocation. Although inhibitory may contribute overall be downstream events NFκB. Since Phe Ter exerted almost same PKA show significant antagonistic effects, suppression might dependent specific adrenergic receptors signaling pathway.