title: Synergy between vitamin D(3) and Toll-like receptor agonists regulates human dendritic cell response during maturation.
abstract: Human dendritic cells (DC) can be differentiated from blood monocytes in the presence of GM-CSF and IL-4 and matured by lipopolysaccharide (LPS). Vitamin D3 inhibits the maturation of human DC measured by changes in surface expression of HLA-DR, CD14, CD40, CD80, CD83, and CD86. We here examine the function of vitamin D3 during DC maturation. One of the earliest changes to LPS-induced maturation was an increase in CD83 expression. Vitamin D3 inhibited the increase in expression of HLA-DR, CD40, CD80, CD83, and CD86 and the decrease in expression of CD14, which was paralleled morphologically by vitamin D3-induced inhibition of dendritic cell differentiation. Vitamin D3 acted in synergy with the TLR agonists LPS and peptidoglycan (PGN) in inducing IL-6, IL-8, and IL-10, whereas vitamin D3 completely inhibited LPS-induced secretion of IL-12. The synergy occurred at concentrations where neither vitamin D3 nor the TLR agonists alone induced measurable cytokine secretion. Both LPS and PGN enhanced the level of the vitamin D3 receptor (VDR). Taken together, these data demonstrated that vitamin D3 and TLR agonists acted in synergy to alter secretion of cytokines from human DC in a direction that may provide an anti-inflammatory environment.
authors.affiliation: Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Brosbøl-Ravnborg
authors.forename: Bettina
authors.initials: B
authors.lastname: Bundgaard
authors.forename: Per
authors.initials: P
authors.lastname: Höllsberg
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004357:Drug Synergism; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010457:Peptidoglycan / Q000494:pharmacology*; D018167:Receptors, Calcitriol / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists* / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D018167:Receptors, Calcitriol; D051193:Toll-Like Receptors; C579457:VDR protein, human; D016753:Interleukin-10; D018664:Interleukin-12; D002762:Cholecalciferol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor