科研之友
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摘要
Neuregulin, previously known as ARIA, is a signaling protein involved in cell survival, synaptic plasticity, cell communication and differentiation. Neuregulin has also been described as a potent inducer of acetylcholine receptor transcription in muscle and although both neuregulin and acetylcholine have been individually described to have neuroprotective roles, their relationship in the cholinergic anti-inflammatory pathway of the brain has not been examined. %26lt;br%26gt;Using three cell lines, BV-2, EOC-20 and RAW 264.7, we investigated the role that neuregulin signaling through the Erb family of tyrosine kinases may play in the anti-inflammatory process mediated by the alpha 7 nicotinic acetylcholine receptors. Here we show that ErbB4 is expressed in all of our cell lines and is phosphorylated upon treatment with neuregulin. Neuregulin treatment further increases the expression of alpha 7 nicotinic acetylcholine receptors in the microglial lines tested. Given the central role of alpha 7 nicotinic acetylcholine receptors in regulating system inflammation we analyzed the expression of several pro-inflammatory cytokines in our system. Using ELISAs for TNF-alpha and IL-6 we show that treatment with NRG can produce a nearly a 33% decrease in the levels of tumor necrosis factor-alpha secreted by activated microglia and a nearly 88% decrease in IL-6. %26lt;br%26gt;Given these results we propose a neuroprotective role for neuregulin wherein it modulates the expression of TNF-alpha and thus inflammation in the CNS via the upregulation of alpha 7 nicotinic acetylcholine receptor expression in microglia in vitro. We suggest that the disregulation of neuregulin expression may be pivotal in neurological disorders characterized by inflammation.
- 出版日期2013-7-30
