Interferon-γ and interferon-β affect endogenous catecholamines in human peripheral blood mononuclear cells:: Implications for multiple sclerosis
Interferon-γ and interferon-β affect endogenous catecholamines in human peripheral blood mononuclear cells:: Implications for multiple sclerosis
复制标题
DOI：
10.1016/j.jneuroim.2005.01.019
复制
发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Lecchini, S
中科院分区：
文献类型：
--
作者：
Cosentino, M;Zaffaroni, M;Lecchini, S
干扰素 (IFN)-γ 在多发性硬化症 (MS) 的发病机制中起着关键作用，而 IFN-β 可能能够改变疾病的临床病程，最终也可以通过抵消 IFN-γ 介导的作用。儿茶酚胺 (CA) 作为神经和免疫系统之间的递质以及免疫细胞中的自分泌/旁分泌介质对免疫反应发挥着重要作用，并且有多项证据支持其与多发性硬化症有关。特别是，多发性硬化症患者的外周血单核细胞 (PBMC) 中似乎出现 CA 产生失调。我们评估了 IFN-β 和 IFN-γ 对 PBMC 中内源性 CA 的影响。在用植物血凝素 (PHA) 刺激的培养 PBMC 中，IFN-β 增加了 CA 的产生并诱导培养基中 CA 的释放，而 IFN-γ 则减少了 CA 的产生和 CA 合成酶酪氨酸羟化酶 mRNA 的表达。与两种 IFN 共孵育可防止 IFN-γ 的抑制作用以及 IFN-β 的刺激作用。 IFN 是第一个被证明可以影响 PBMC 中内源性 CA 的生理化合物：鉴于 CA 依赖性机制在免疫反应中的作用，这些发现可能有助于更好地理解 IFN-β 作为 MS 免疫调节药物的作用机制。 (C) 2005 Elsevier B.V. 保留所有权利。
Interferon (IFN)-gamma plays a -pivotal role in the pathogenesis of multiple sclerosis (MS), while IFN-beta may be able to modify the clinical course of the disease, eventually also by counterbalancing IFN-gamma-mediated effects. Catecholamines (CA) exert important effects on the immune response, both as transmitters between the nervous and the immune system, as well as autocrine/paracrine mediators in immune cells, and several lines of evidence support their involvement in MS. In particular, dysregulated production of CA seems to occur in peripheral blood mononuclear cells (PBMCs) of MS patients. We assessed the effects of IFN-beta and IFN-gamma on endogenous CA in PBMCs. In cultured PBMCs stimulated with phytohaemagglutinin (PHA), IFN-beta increased CA production and induced CA release in the culture medium, while IFN-gamma decreased both CA production and the expression of mRNA for the CA-synthesizing enzyme tyrosine hydroxylase. Coincubation with both IFNs prevented the inhibitory effect of IFN-gamma, as well as the stimulatory effect of IFN-beta. IFNs are the first physiological compounds shown to affect endogenous CA in PBMCs: in view of the role of CA-dependent mechanisms in the immune response, these findings may help to better understand the mechanisms of action of IFN-beta as an immunomodulatory drug in MS. (C) 2005 Elsevier B.V. All rights reserved.