Liver-X-receptor activator prevents homocysteine-induced production of IgG antibodies from murine B lymphocytes via the ROS-NF-κB pathway
Liver-X-receptor activator prevents homocysteine-induced production of IgG antibodies from murine B lymphocytes via the ROS-NF-κB pathway
复制标题
DOI：
10.1016/j.bbrc.2007.04.016
复制
发表时间：
2007-06-08
影响因子：
3.1
通讯作者：
Wang, Xian
中科院分区：
文献类型：
--
作者：
Chang, Lina;Zhang, Zhenmin;Wang, Xian
我们之前的研究表明，同型系统氨酸（Hcy）促进小鼠脾B淋巴细胞的增殖。在这项研究中，我们研究了Hcy是否能刺激IgG抗体的产生。Hcy显著增加静止B淋巴细胞IgG抗体的产生。apoe基因敲除小鼠高同型半胱氨酸血症的B淋巴细胞在基础Hcy水平或对脂多糖的反应中显示IgG分泌升高。MnTMPyP促进活性氧（ROS）的形成和自由基清除剂，减少hcy诱导的IgG分泌。NF-kappa B抑制剂（MG132）也显著降低hcy诱导的IgG分泌。此外，hcy诱导的ROS的形成、nf - κ B的激活和IgG的分泌可以被肝x受体（LXR）激动剂TO 901317抑制。因此，我们的数据提供了强有力的证据，证明HHcy在体外和体内诱导小鼠脾B淋巴细胞产生IgG。其作用机制可能是通过ROS-NF-kappa B通路，并可通过LXR的激活而减弱。(c) 2007爱思唯尔公司版权所有。
Our previous study showed that homosysteine (Hcy) promotes proliferation of mouse splenic B lymphocytes. In this study, we investigated whether Hcy could stimulate the production of IgG antibodies. Hcy significantly increased the production of IgG antibodies from resting B lymphocytes. B lymphocytes from ApoE-knockout mice with hyperhomocysteinemia showed elevated IgG secretion at either the basal Hcy level or in response to lipopolysaccharide. Hey promoted reactive oxygen species (ROS) formation, and free radical scavengers, MnTMPyP decreased Hcy-induced IgG secretion. The inhibitor of NF-kappa B (MG132) also significantly reduced Hcy-induced IgG secretion. Furthermore, Hcy-induced formation of ROS, activation of NF-kappa B, and secretion of IgG could be inhibited by the liver-X-receptor (LXR) agonist TO 901317. Thus, our data provide strong evidence that HHcy induces IgG production from murine splenic B lymphocytes both in vitro and in vivo. The mechanism might be through the ROS-NF-kappa B pathway and can be attenuated by the activation of LXR. (c) 2007 Elsevier Inc. All rights reserved.