Journal of cellular physiology
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The phosphorylation of c-jun N-terminal kinase (JNK) and the subsequent production of C-C chemokine CCL2 (monocyte chemoattractant protein; MCP-1) in spinal astrocytes contribute to the initiation of neurological disorders including chronic pain. Astrocytes express neurotransmitter receptors which could be targeted to ameliorate neurological disorders. In the current study, the involvement of the β-adrenergic system in the regulation of JNK activity and CCL2 production after stimulation with tumor necrosis factor (TNF)-α, one of many initiators of neuroinflammation, was elucidated. ⋯ The TNF-α-induced JNK1 phosphorylation was significantly blocked by treatment with GSK-3β inhibitors (either LiCl or TWS119), and stimulation of β-adrenergic receptors induced the inhibition of GSK-3β through the phosphorylation of Ser(9). Moreover, treatment with isoproterenol markedly suppressed the TNF-α-induced increase of CCL2 mRNA expression and CCL2 production through a β-adrenergic receptor-PKA pathway mediated by GSK-3β regulation. Thus, activation of β1/2 adrenergic receptors expressed in spinal astrocytes could be a novel method of moderating neurological disorders with endogenous catecholamines or selective agonists.