title: Differential effects of statins on relevant functions of human monocyte-derived dendritic cells.
abstract: Statins were shown to possess immunomodulating properties, but the mechanisms of statin effects on the immune system are poorly understood. We analyzed the influence of statins on professional antigen-presenting dendritic cells (DC). Immature DC were cultivated from monocytes of healthy donors. DC maturation was induced by lipopolysaccharide (LPS; 1 microg/mL). Unstimulated and LPS-stimulated DC were treated with simvastatin or atorvastatin (0.1-1 microM). The expression of CD40, CD83, CD86, and human leukocyte antigen-DR on unstimulated and LPS-stimulated DC was reduced significantly by statins, and the expression of Toll-like receptor 2 (TLR2) and TLR4 on LPS-stimulated DC was enhanced temporarily. Statins caused a significant reduction of endocytosis of fluorescein isothiocyanate-dextran by DC. Statins significantly inhibited the basal secretion of interleukin (IL)-6, IL-8, IL-12, and tumor necrosis factor alpha from unstimulated DC, and their release from LPS-stimulated DC was enhanced. In mixed leukocyte reaction, preincubation of LPS-stimulated DC with statins significantly suppressed their clustering with T cells and their ability to induce T cell proliferation, CD71, and CD25 up-regulation on T cells and the secretion of interferon-gamma and IL-2 from T cells. In conclusion, this study showed that statins suppressed endocytosis, basal secretion of proinflammatory cytokines, and the ability of DC to induce T cell proliferation, activation, and T helper cell type 1 differentiation. However, statin preincubation of LPS-stimulated DC caused a further increase in their secretion of proinflammatory cytokines.
authors.affiliation: Medical Clinic II, Department of Dermatology, University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. A.Yilmaz.med2.uni-erlangen@email.de
authors.forename: Atilla
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Christine
authors.initials: C
authors.lastname: Reiss
authors.forename: Alexander
authors.initials: A
authors.lastname: Weng
authors.forename: Iwona
authors.initials: I
authors.lastname: Cicha
authors.forename: Christian
authors.initials: C
authors.lastname: Stumpf
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinkasserer
authors.forename: Werner G
authors.initials: WG
authors.lastname: Daniel
authors.forename: Christoph D
authors.initials: CD
authors.lastname: Garlichs
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D000954:Antigens, Surface / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D051193:Toll-Like Receptors / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors