维生素D3对单核细胞和巨噬细胞中单核细胞趋化蛋白1产生的影响。
Effect of Vitamin D3 on Monocyte Chemoattractant Protein 1 Production in Monocytes and Macrophages.
作者信息
Wang Yi-Chen, Hsieh Chong-Chao, Kuo Hsuan-Fu, Tsai Ming-Kai, Yang San-Nan, Kuo Chang-Hung, Lee Min-Sheng, Hung Chih-Hsing
机构信息
Division of Cardiology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital;
Division of Cardiac Surgery, Department of Surgery;
出版信息
Acta Cardiol Sin. 2014 Mar;30(2):144-50.
BACKGROUND
Chemokine is important in the initiation and progression of atherosclerosis, the clinically manifest stages of atherosclerosis and acute coronary syndrome. Vitamin D deficiency has been reportedly linked with hypertension and myocardial infarction, as well as other cardiovascular-related diseases, such as congestive heart failure, peripheral vascular disease and atherosclerosis. Monocyte chemoattractant protein 1 (MCP-1) mediates atherosclerosis and other cardiovascular diseases. However, there have been few studies conducted about the role of 1α,25-(OH)2D3 on MCP-1 expression in human monocytes.
METHODS
We investigated the effects of vitamin A, C and 1α,25-(OH)2D3, three common vitamins, to better ascertain MCP-1 expression in human monocyte and also the associated intracellular mechanism. Human monocyte cell line (THP-1 cell) and THP-1 cell-induced macrophage were treated with varying doses of vitamin A, C and 1α,25-(OH)2D3 for 2 hours before LPS stimulation. Supernatants were harvested to measure MCP-1 levels by the enzyme-linked immunosorbent assay (ELISA). The intracellular mechanism about the effects of vitamin A, C and 1α,25-(OH)2D3 on the expression of MCP-1 expression in human monocytes was assessed by western blot.
RESULTS
We found that Lipopolysaccharides (LPS)-induced MCP-1 production was suppressed by 1α,25-(OH)2D3 in THP-1 cells and THP-1-induced macrophage. Only high concentration of vitamin A and C could reduce LPS-induced MCP-1 production in THP-1-induced macrophage, but not in THP-1 cells. LPS-induced p38 expression in THP-1 cells was suppressed by 1α,25-(OH)2D3. A selective p38 pathway inhibitor SB203580 could also suppress LPS-induced MCP-1 production. However, vitamin D receptor blocking antibody could reverse the suppressive effect of 1α,25-(OH)2D3 on MCP-1 expression.
CONCLUSIONS
These data demonstrate that 1α,25-(OH)2D3 is effective in down-regulating LPS-induced MCP-1. The suppressive effect on MCP-1 may, at least in part, involve the vitamin D receptor and down-regulation of LPS - induced p38 expression.
KEY WORDS
Chemokine; Monocyte chemoattractant protein 1 (MCP-1); Monocyte; p38; Vitamin D.
背景
趋化因子在动脉粥样硬化的发生发展、动脉粥样硬化的临床显性阶段及急性冠脉综合征中起重要作用。据报道，维生素D缺乏与高血压、心肌梗死以及其他心血管相关疾病有关，如充血性心力衰竭、外周血管疾病和动脉粥样硬化。单核细胞趋化蛋白1（MCP-1）介导动脉粥样硬化及其他心血管疾病。然而，关于1α,25-（OH）2D3对人单核细胞中MCP-1表达的作用，相关研究较少。
方法
我们研究了维生素A、C和1α,25-（OH）2D3这三种常见维生素的作用，以更好地确定人单核细胞中MCP-1的表达及其相关的细胞内机制。在脂多糖（LPS）刺激前，用不同剂量的维生素A、C和1α,25-（OH）2D3处理人单核细胞系（THP-1细胞）和THP-1细胞诱导的巨噬细胞2小时。收集上清液，通过酶联免疫吸附测定（ELISA）测量MCP-1水平。通过蛋白质印迹法评估维生素A、C和1α,25-（OH）2D3对人单核细胞中MCP-1表达影响的细胞内机制。
结果
我们发现，1α,25-（OH）2D3可抑制THP-1细胞和THP-1诱导的巨噬细胞中脂多糖（LPS）诱导的MCP-1产生。只有高浓度的维生素A和C可降低THP-1诱导的巨噬细胞中LPS诱导的MCP-1产生，但对THP-1细胞无效。1α,25-（OH）2D3可抑制THP-1细胞中LPS诱导的p38表达。选择性p38通路抑制剂SB203580也可抑制LPS诱导的MCP-1产生。然而，维生素D受体阻断抗体可逆转1α,25-（OH）2D3对MCP-1表达的抑制作用。
结论
这些数据表明，1α,25-（OH）2D3可有效下调LPS诱导的MCP-1。对MCP-1的抑制作用可能至少部分涉及维生素D受体以及LPS诱导的p38表达下调。
关键词
趋化因子；单核细胞趋化蛋白1（MCP-1）；单核细胞；p38；维生素D
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