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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Immune modulatory effects of statins
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Immune modulatory effects of statins

机译：他汀类药物的免疫调节效应

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摘要

Despite major advances in recent years, immunosuppressive regimens for multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and graft-versus-host disease still have major adverse effects and immunomodulation rather than immune paralysis would be desirable. Statins inhibit the rate-limiting enzyme of the L-mevalonate pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. It was shown that blocking the L-mevalonate pathway reduces inflammation through effects on downstream metabolites of the pathway including farnesylpyrophosphates and geranylgeranylpyrophosphates, which are essential for the attachment of GTPases like RhoA, Rac and Ras to the cell membrane. Therefore, L-mevalonate pathway downstream products play critical roles in the different steps of an immune response including immune cell activation, migration, cytokine production, immune metabolism and survival. This review discusses the relevance of the different metabolites for the immunomodulatory effect of statins and connects preclinical results with data from clinical studies that tested statins for the treatment of different inflammatory diseases.
机译：尽管近年来重大进展，但多发性硬化症的免疫抑制方案，类风湿性关节炎，全身性红斑狼疮和移植物与宿主病仍然具有主要的不利影响和免疫调节而不是免疫瘫痪。他汀汀汀抑制了L-甲戊酯途径的速率限制酶，3-羟基-3-甲基 - 谷族 - 辅酶A还原酶。结果表明，阻断L-Mevalonate途径通过对途径的下游代谢产物对包括法呢基磷酸酯和甲苯基甲基苯磷酸酯的影响来减少炎症，这对于将GTP酶如RhoA，RAC和Ras附着到细胞膜是必不可少的。因此，L-Mevalonate途径下游产品在免疫应答的不同步骤中起重要作用，包括免疫细胞活化，迁移，细胞因子产生，免疫代谢和存活。本综述讨论了不同代谢产物对他汀类药物调节作用的相关性，并将临床前结果与来自测试他汀类药物治疗不同炎症性疾病的临床研究的临床研究。

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