Lovastatin inhibits bone marrow-derived dendritic cell maturation and upregulates proinflammatory cytokine production
Lovastatin inhibits bone marrow-derived dendritic cell maturation and upregulates proinflammatory cytokine production
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DOI：
10.1016/s0008-8749(03)00148-5
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发表时间：
2003-05-01
影响因子：
4.3
通讯作者：
Fernandes, G
中科院分区：
文献类型：
--
作者：
Sun, DX;Fernandes, G
他汀类药物是一组羟甲基戊二酰辅酶a （HMG-CoA）还原酶抑制剂，是最有效的降脂药物，目前在临床上被广泛使用。最近，也有研究表明他汀类药物会影响免疫反应。我们研究了洛伐他汀对骨髓源性树突状细胞（BM-DC）成熟和功能变化的影响。洛伐他汀以剂量依赖性的方式抑制DC上MHC 11类和CD40的表达，但对CD16、CD80、CD86和CD11b的表达影响较小。洛伐他汀处理的DC核提取物降低了NF-kappaB DNA结合活性。虽然洛伐他汀不影响DC的抗原捕获能力，但DC的t细胞刺激活性受到抑制。通过细胞内细胞因子染色、ELISA和cDNA芯片检测，洛伐他汀上调LPS诱导的DC促炎细胞因子的产生。在体外添加甲羟戊酸钠可以防止这些影响。这些结果表明洛伐他汀可能通过甲羟戊酸依赖途径抑制BM-DC成熟并上调细胞因子的产生，并可能对先天或适应性免疫产生不利影响。(C) 2003 Elsevier Science（美国）版权所有。
Statins are a group of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors which are most effective as lipid lowering agents, and are currently extensively used clinically. Recently, it was also shown that statins affect the immune response. We investigated the effects of lovastatin on the maturation and functional changes of bone marrow-derived dendritic, cells (BM-DC). Lovastatin inhibited MHC class 11 and CD40 expression on DC in a dose-dependent manner, but had lesser effects on CD16, CD80, CD86, and CD11b expression. Nuclear extracts of lovastatin treated DC had decreased NF-kappaB DNA binding activity. Although antigen capture capacity of DC was not affected by lovastatin, the T-cell stimulatory activity of DC was inhibited. Lovastatin upregulated DC pro-inflammatory cytokine production induced by LPS as measured by intracellular cytokine staining, ELISA and cDNA microarrays. Mevalonate, added in vitro, prevented these effects. These results indicate that lovastatin may inhibit BM-DC maturation and up-regulate cytokine production through a mevalonate dependent pathway, and may cause adverse effects on either innate or adaptive immunity. (C) 2003 Elsevier Science (USA). All rights reserved.