title: Effects of vitamin D3, calcipotriol and FTY720 on the expression of surface molecules and cytolytic activities of human natural killer cells and dendritic cells.
abstract: We describe here the effects of three drugs that are either approved or have the potential for treating multiple sclerosis (MS) patients through the in vitro activities of human natural killer (NK) cells and dendritic cells (DCs). Our results indicate that 1,25(OH)2D3, the biologically active metabolite of vitamin D3, calcipotriol and FTY720 augment IL-2-activated NK cell lysis of K562 and RAJI tumor cell lines as well as immature (i) and mature (m) DCs, with variable efficacies. These results are corroborated with the ability of the drugs to up-regulate the expression of NK cytotoxicity receptors NKp30 and NKp44, as well as NKG2D on the surfaces of NK cells. Also, they down-regulate the expression of the killer inhibitory receptor CD158. The three drugs down-regulate the expression of CCR6 on the surface of iDCs, whereas vitamin D3 and calcipotriol tend to up-regulate the expression of CCR7 on mDCs, suggesting that they may influence the migration of DCs into the lymph nodes. Finally, vitamin D3, calcipotriol and FTY720 enhance NK17/NK1 cell lysis of K562 cells, suggesting that a possible mechanism of action for these drugs is via activating these newly described cells. In conclusion, our results show novel mechanisms of action for vitamin D3, calcipotriol and FTY720 on cells of the innate immune system.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1103, Oslo N-0317, Norway. azzam.maghazachi@medisin.uio.no.
authors.forename: Zaidoon
authors.initials: Z
authors.lastname: Al-Jaderi
authors.forename: Azzam A
authors.initials: AA
authors.lastname: Maghazachi
mesh_terms: D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D015536:Down-Regulation; D000068876:Fingolimod Hydrochloride; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000188:drug therapy; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000235:genetics / Q000378:metabolism; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000235:genetics / Q000378:metabolism; D011409:Propylene Glycols / Q000494:pharmacology*; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C106311:CCR6 protein, human; C515370:CCR7 protein, human; D007376:Interleukin-2; C527085:KLRK1 protein, human; D008565:Membrane Proteins; C112837:NCR2 protein, human; C431710:NCR3 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D011409:Propylene Glycols; D054399:Receptors, CCR6; D054400:Receptors, CCR7; C055085:calcipotriene; D002762:Cholecalciferol; D002117:Calcitriol; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine