HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new implications for atherosclerosis

被引:122
作者
Yilmaz, A
Reiss, C
Tantawi, O
Weng, A
Stumpf, C
Raaz, D
Ludwig, J
Berger, T
Steinkasserer, A
Daniel, WG
Garlichs, CD
机构
[1] Univ Erlangen Nurnberg, Med Clin 2, D-91054 Erlangen, Germany
[2] Univ Erlangen Nurnberg, Dept Dermatol, D-91052 Erlangen, Germany
关键词
atherosclerosis; inflammation; immunology; dendritic cells; statins;
D O I
10.1016/j.atherosclerosis.2003.10.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The beneficial effects of statins in atherosclerosis have been partly attributed to their immunomodulating functions. Dendritic cells (DC), which are "professional" antigen-presenting cells, were recently detected in atherosclerotic plaques. It is assumed that DC play a critical role in the immunological processes related to atherosclerosis. Thus, we investigated the effects of statins on maturation and antigen-presenting function of DC. Human monocyte-derived DC were incubated with simvastatin or atorvastatin (1-10 muM) for different periods (1-48 h), and were subsequently stimulated with a cytokine cocktail (1.25 ng/ml TNF-alpha, 1 ng/ml II-1beta, and 0.5 mug/ml prostaglandin E-2) to induce maturation. In contrast to untreated DC, statin-preincubated DC exhibited an immature phenotype and a significantly lower expression of the maturation-associated markers CD83, CD40, CD86, HLA-DR, and CCR7. The inhibitory statin effect was completely reversed by mevalonate or geranylgeranyl pyrophosphate. In addition, preincubation with statins significantly reduced the ability of cytokine-stimulated DC to induce T cell proliferation. In the present study, we have shown that statins inhibit the maturation and antigen-presenting function of human myeloid dendritic cells, thus maybe contributing to their beneficial effects in atherosclerosis. Therefore, the use of statins as immunomodulators might also provide a new therapeutic approach to other immunological disorders. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:85 / 93
页数:9
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