HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new implications for atherosclerosis
2003; Elsevier BV; Volume: 172; Issue: 1 Linguagem: Inglês
10.1016/j.atherosclerosis.2003.10.002
ISSN1879-1484
AutoresAtilla Yılmaz, Christine Reiss, Omeima Tantawi, Alexander Weng, Christian Stumpf, Dorette Raaz, Josef Ludwig, Thomas G. Berger, Alexander Steinkasserer, Werner G. Daniel, Christoph D. Garlichs,
Tópico(s)Inflammatory mediators and NSAID effects
ResumoThe 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 (1-10microM) for different periods (1-48h), and were subsequently stimulated with a cytokine cocktail (1.25ng/ml TNF-alpha, 1ng/ml Il-1beta, and 0.5microg/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.
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