L-cystathionine inhibits oxidized low density lipoprotein-induced THP-1-derived macrophage inflammatory cytokine monocyte chemoattractant protein-1 generation via the NF-κB pathway.

L-cystathionine inhibits oxidized low density lipoprotein-induced THP-1-derived macrophage inflammatory cytokine monocyte chemoattractant protein-1 generation via the NF-κB pathway.
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L-胱硫醚通过 NF-kappa B 途径抑制氧化低密度脂蛋白诱导的 THP-1 衍生巨噬细胞炎症细胞因子单核细胞趋化蛋白-1 的产生

DOI:
10.1038/srep10453
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发表时间:
2015-05-28
期刊:
影响因子:
4.6
通讯作者:
Jin H
Jin H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhu M;Du J;Liu AD;Holmberg L;Chen SY;Bu D;Tang C;Jin H

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本研究旨在探讨l -胱硫氨酸是否以及如何对体外氧化低密度脂蛋白(ox-LDL)刺激培养的thp -1来源的巨噬细胞的炎症反应有调节作用。体外培养人单核细胞THP-1细胞,经PMA诱导24小时后分化为巨噬细胞。用l -胱硫氨酸预处理巨噬细胞,然后用ox-LDL处理。结果显示,与对照组相比,ox-LDL刺激可通过增强NF-κB p65磷酸化、核易位和MCP-1启动子DNA结合,显著上调thp -1源性巨噬细胞MCP-1的表达。与ox-LDL组相比,0.3 mmol/L和1.0 mmol/L L-半胱硫氨酸显著抑制thp -1源性巨噬细胞MCP-1的表达。机制上,0.3 mmol/L和1.0 mmol/L L-半胱硫氨酸抑制了NF-κB p65蛋白的磷酸化和核易位,以及NF-κB与MCP-1启动子的DNA结合活性和DNA结合水平,导致thp -1源性巨噬细胞MCP-1生成减少。本研究提示l -胱硫氨酸可通过抑制NF-κB p65磷酸化、核易位和进入细胞核后MCP-1启动子序列的结合,抑制ox-LDL诱导的thp -1源性巨噬细胞中MCP-1的表达。
This study aimed to explore whether and how L-cystathionine had any regulatory effect on the inflammatory response in THP-1-derived macrophages culturedin vitrounder oxidized low-density lipoprotein (ox-LDL) stimulation. The human monocyte line THP-1 cell was culturedin vitroand differentiated into macrophages after 24 hours of PMA induction. Macrophages were pretreated with L-cystathionine and then treated with ox-LDL. The results showed that compared with the controls, ox-LDL stimulation significantly upregulated the expression of THP-1-derived macrophage MCP-1 by enhancing NF-κB p65 phosphorylation, nuclear translocation and DNA binding with the MCP-1 promoter. Compared with the ox-LDL group, 0.3 mmol/L and 1.0 mmol/L L-cystathionine significantly inhibited the expression of THP-1-derived macrophage MCP-1. Mechanistically, 0.3 mmol/L and 1.0 mmol/L L-cystathionine suppressed phosphorylation and nuclear translocation of the NF-κB p65 protein, as well as the DNA binding activity and DNA binding level of NF-κB with the MCP-1 promoter, which resulted in a reduced THP-1-derived macrophage MCP-1 generation. This study suggests that L-cystathionine could inhibit the expression of MCP-1 in THP-1-derived macrophages induced by ox-LDL via inhibition of NF-κB p65 phosphorylation, nuclear translocation and binding of the MCP-1 promoter sequence after entry into the nucleus.
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