Douglas S A, Bunn S J
Centre for Neuroendocrinology and Department of Anatomy and Structural Biology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
J Neuroendocrinol. 2009 Mar;21(3):200-7. doi: 10.1111/j.1365-2826.2009.01821.x.
Adrenal medullary chromaffin cells are an integral part of the neuroendocrine system, playing an important role in the physiological adaptation to stress. In response to a wide variety of stimuli, including acetylcholine released from the splanchnic nerve, hormones such as angiotensin II or paracrine signals such as prostaglandins, chromaffin cells synthesise and secrete catecholamines and a number of biologically active peptides. This adrenal medullary output mediates a complex and diverse stress response. We report that chromaffin cells also respond both acutely and chronically to interferon (IFN)-alpha, thus providing a mechanism of interaction between the immune system and the stress response. Incubation of isolated bovine chromaffin cells maintained in culture, with IFN-alpha resulted in a rapid, transient activation of the extracellular signal-regulated protein kinase (ERK)1/2, which was maximal after 5 min. IFN-alpha mediated activation of ERK1/2 appeared to be responsible for the increased phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This tyrosine hydroxylase phosphorylation was exclusively on serine 31, with no change in the phosphorylation of serine 19 or 40. This increase in the serine 31 phosphorylation of tyrosine hydroxylase was prevented by inhibition of protein kinase C or ERK1/2 activation. Incubation with IFN-alpha also resulted in a time- and concentration-dependent phosphorylation and nuclear translocation of signal transducer and activator of transcription proteins (STAT)1 and 2. This response was maximal after approximately 60 min. Prolonged treatment with IFN-alpha (12-48 h) resulted in increased expression of STAT1 and, to a lesser extent, STAT2. Thus, these findings demonstrate that adrenal medullary chromaffin cells are responsive to IFN-alpha and provide a possible cellular mechanism by which this immune-derived signal can potentially influence and integrate with the stress response.
肾上腺髓质嗜铬细胞是神经内分泌系统的一个组成部分，在对应激的生理适应中发挥重要作用。响应包括内脏神经释放的乙酰胆碱、血管紧张素II等激素或前列腺素等旁分泌信号在内的多种刺激，嗜铬细胞合成并分泌儿茶酚胺和一些生物活性肽。这种肾上腺髓质输出介导了复杂多样的应激反应。我们报告嗜铬细胞也对α干扰素（IFN-α）产生急性和慢性反应，从而提供了免疫系统与应激反应之间的一种相互作用机制。用IFN-α孵育培养的分离牛嗜铬细胞，导致细胞外信号调节蛋白激酶（ERK）1/2迅速、短暂激活，5分钟后达到最大值。IFN-α介导的ERK1/2激活似乎是儿茶酚胺合成限速酶酪氨酸羟化酶磷酸化增加的原因。这种酪氨酸羟化酶磷酸化仅发生在丝氨酸31上，丝氨酸19或40的磷酸化没有变化。抑制蛋白激酶C或ERK1/2激活可阻止酪氨酸羟化酶丝氨酸31磷酸化的增加。用IFN-α孵育还导致信号转导和转录激活蛋白（STAT）1和2发生时间和浓度依赖性的磷酸化及核转位。该反应在约60分钟后达到最大值。用IFN-α长期处理（12 - 48小时）导致STAT1表达增加，STAT2表达也有较小程度增加。因此，这些发现表明肾上腺髓质嗜铬细胞对IFN-α有反应，并提供了一种可能的细胞机制，通过该机制这种免疫衍生信号可能影响应激反应并与之整合。
