Song Zhenyuan, Chen Theresa, Deaciuc Ion V, Uriarte Silvia, Hill Daniell, Barve Shirish, McClain Craig J
Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Cytokine. 2004 Dec 21;28(6):214-23. doi: 10.1016/j.cyto.2004.08.004.
Interleukin-6 (IL-6) is a multifunctional cytokine having primarily anti-apoptotic and anti-inflammatory effects. Recent reports have documented that IL-6 plays a key role in liver regeneration. Intracellular deficiency of S-adenosylmethionine (SAMe) is a hallmark of toxin-induced liver injury. Although the administration of exogenous SAMe attenuates liver injury, its mechanisms of action are not fully understood. Here we investigated the effects of exogenous SAMe on IL-6 production in monocytes and Kupffer cells. RAW 264.7 cells, a murine monocyte cell line, and isolated rat Kupffer cells were stimulated with lipopolysaccharide (LPS) in the absence or presence of exogenous SAMe. IL-6 production was assayed by ELISA and intracellular SAMe concentrations were measured by HPLC. We have found that exogenous SAMe administration enhanced both IL-6 protein production and gene expression in LPS-stimulated monocytes and Kupffer cells. Cycloleucine (CL), an inhibitor for extrahepatic methionine adenosyltransferases (MAT), inhibited LPS-stimulated IL-6 production. The enhancement of LPS-stimulated IL-6 production by SAMe was inhibited by ZM241385, a specific antagonist of adenosine (A2) receptor. Our results demonstrate that SAMe administration may exert its anti-inflammatory and hepatoprotective effects, at least in part, by enhancing LPS-stimulated IL-6 production.
白细胞介素-6（IL-6）是一种多功能细胞因子，主要具有抗凋亡和抗炎作用。最近的报道表明，IL-6在肝脏再生中起关键作用。细胞内S-腺苷甲硫氨酸（SAMe）缺乏是毒素诱导的肝损伤的一个标志。尽管外源性SAMe的给药可减轻肝损伤，但其作用机制尚未完全了解。在此，我们研究了外源性SAMe对单核细胞和库普弗细胞中IL-6产生的影响。在不存在或存在外源性SAMe的情况下，用脂多糖（LPS）刺激RAW 264.7细胞（一种小鼠单核细胞系）和分离的大鼠库普弗细胞。通过ELISA测定IL-6的产生，并通过HPLC测量细胞内SAMe浓度。我们发现，外源性SAMe给药增强了LPS刺激的单核细胞和库普弗细胞中IL-6蛋白的产生和基因表达。环亮氨酸（CL）是一种肝外甲硫氨酸腺苷转移酶（MAT）的抑制剂，可抑制LPS刺激的IL-6产生。SAMe对LPS刺激的IL-6产生的增强作用被腺苷（A2）受体的特异性拮抗剂ZM241385抑制。我们的结果表明，SAMe给药可能至少部分地通过增强LPS刺激的IL-6产生来发挥其抗炎和肝保护作用。
