1-alpha-calcidol modulates major human monocyte antigens and toll-like receptors TLR 2 and TLR4 in vitro.
Since vitamin D derivatives are known to interfere with the cellular immune response, we analysed the possible effect of 1-alpha-calcidol (AC) on major monocyte antigens CD14 (an endotoxin receptor), HLA-DR, and toll-like recptors 2 and 4 (TLR2, TLR4). Peripheral blood monocytes were isolated from healthy donors and cultured by standard protocol followed by incubation with various concentrations of AC in unstimulated and LPS-activated cells. After 24, 48 and 72 hours cells were harvested and analysed for the expression of antigens by flowcytometry. Compared to the controls AC increased the expression of CD14 in a dose and time dependent manner (after 72 hours culture time p < 0.01). AC was capable of further stimulating CD14 expression in LPS activated monocytes (p < 0.05). Both LPS and AC downmodulated HLA-DR dramatically after 24 (p < 0.05), 48 (p < 0.01) and 72 hours (p < 0.0001). The expression of TLR2 but not of TLR4 was inhibited by 10-7M AC. The data reveal that AC significantly modulates the expression of CD14, HLA-DR as well as of TLR2, all involved as targets and effector molecules in antigen recognition and processing, relevant to overcome infections and organ lesions.
Scherberich
J E
JE
Department Nephrology and Hypertension, Hospital München-Harlaching, Teaching Hospital, Ludwig-Maxmilians-University, Munich, Germany. J.Scherberich@web.de
Kellermeyer
M
M
Ried
C
C
Hartinger
A
A
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D016588:Anticarcinogenic Agents; D006684:HLA-DR Antigens; D006887:Hydroxycholecalciferols; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C008088:alfacalcidol