Departament de Biologia Cel·lular, Facultat de Biologia, Universitat de Barcelona , Barcelona , Spain.
Free Radic Res. 2014 Feb;48(2):119-28. doi: 10.3109/10715762.2013.845295. Epub 2013 Oct 11.
Melatonin has been shown to down-regulate inflammatory responses and provide neuroprotection. However, the mechanisms underlying the anti-inflammatory properties of melatonin are poorly understood. In the present work, we studied the modulatory effect of melatonin against pro-inflammatory cytokines in glial cell cultures. Treatment with pro-inflammatory cytokines mainly tumor necrosis factor-alpha, interleukin 1-beta, and interferon-gamma induces an increase in inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. Pre-treatment with melatonin produced an inhibitory effect on iNOS expression and NO production. The biochemical studies revealed that cytokine treatment favors the activation of several pathways, such as mitogen-activated protein kinases (MAPKs), STAT1, and STAT3; however, the anti-inflammatory effect of melatonin was accompanied only by a decrease in p38 MAPK activity. Likewise, SB203580 a p38 kinase inhibitor inhibits NO production. These data indicate that the anti-inflammatory action of melatonin in glial cells after stimulation with pro-inflammatory cytokines may be in part, attributable to p38 inhibition which down-regulates iNOS expression and NO production.
褪黑素已被证明可下调炎症反应并提供神经保护。然而，褪黑素抗炎特性的机制尚不清楚。在本工作中，我们研究了褪黑素对神经胶质细胞培养物中促炎细胞因子的调节作用。促炎细胞因子（主要是肿瘤坏死因子-α、白细胞介素 1-β 和干扰素-γ）的处理会诱导诱导型一氧化氮合酶（iNOS）的表达和一氧化氮（NO）的产生增加。褪黑素预处理对 iNOS 的表达和 NO 的产生有抑制作用。生化研究表明，细胞因子处理有利于丝裂原激活蛋白激酶（MAPKs）、STAT1 和 STAT3 等多种途径的激活；然而，褪黑素的抗炎作用仅伴有 p38 MAPK 活性的降低。同样，p38 激酶抑制剂 SB203580 可抑制 NO 的产生。这些数据表明，褪黑素在受到促炎细胞因子刺激后的神经胶质细胞中的抗炎作用可能部分归因于 p38 的抑制，该抑制可下调 iNOS 的表达和 NO 的产生。
