Liposomal incorporation changes the effect of 1.25-dihydroxyvitamin D3 on the phospholipase C signal transduction pathway and the eicosanoid cascade on keratinocytes in vitro.
1.25-dihydroxyvitamin D3 is of clinical importance (e.g. in the treatment of psoriasis) given its ability to regulate the proliferation and differentiation of human keratinocytes. 1.25-Dihydroxyvitamin D3 mediates its action via genomic and nongenomic pathways. The nongenomic actions begin with the activation of phospholipase C and the subsequent rapid rise in calcium within the cells. We incorporated 1.25-dihydroxyvitamin D3 in liposomes of varying compositions in an attempt to improve their effect/negative side effect ratio. The influence of empty liposomes (1 mM) and free and liposomally incorporated 1.25-dihydroxyvitamin D3 (10 nM) on the rapid release of sulfidoleucotrien and inositole 1,4,5 triphosphate was examined in keratinocytes in vitro. Free 10 nM 1.25-dihydroxyvitamin D3 provoked a rapid rise in sulfidoleucotriens within 30 seconds, followed by a swift decrease in sulfidoleucotrien and inositole 1,4,5-triphosphate concentration after 10 minutes. Empty liposomes and liposomal-incorporated 1.25-dihydroxyvitamin D3 did not show such a strong effect. These results suggest the occurrence of specific binding sites for 1.25-dihydroxyvitamin D3 on the membrane level that are incapable of recognizing 1.25-dihydroxyvitamin D3 trapped within liposomal membrane.
Prüfer
K
K
Department of Anatomy II, University of Jena, Germany.
Jirikowski
G F
GF
D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D015777:Eicosanoids / Q000378:metabolism*; D004790:Enzyme Induction; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000096:biosynthesis*
D015777:Eicosanoids; D015289:Leukotrienes; D008081:Liposomes; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002117:Calcitriol