Calcipotriol inhibits the proliferation of hyperproliferative CD29 positive keratinocytes in psoriatic epidermis in the absence of an effect on the function and number of antigen-presenting cells.
The aim of this study was to elucidate some of the possible mechanisms of action of the vitamin D analogue calcipotriol in vivo. Calcipotriol is finding increasing use in the treatment of psoriasis, but the primary target cell in vivo has not yet been identified. We treated psoriatic patients and healthy volunteers with calcipotriol and placebo ointment for 4 and 7 days, and obtained epidermal cell suspensions from treated areas. Epidermal cells were cocultured with autologous T cells, isolated from peripheral blood, in the absence or the presence of a classical antigen or a superantigen. In both psoriatic and normal skin, calcipotriol treatment did not alter the capacity of epidermal antigen-presenting cells to stimulate the proliferation of autologous T cells, either in the absence or in the presence of exogenous antigen. Epidermal cell suspensions were analysed further by staining for infiltrating leucocytes (CD45+) and Langerhans cells (CD1a+). Flow cytometric analysis showed that calcipotriol did not alter the number of CD45+ cells or Langerhans cells in psoriatic skin. These results indicate that calcipotriol does not alter either the number of the function of epidermal antigen-presenting cells in psoriatic epidermis. In contrast, we found that calcipotriol significantly inhibited the proliferation of epidermal cells isolated from psoriatic skin after in vivo treatment, as determined by propidium iodide staining and flow cytometry. More specifically, we stained for CD29+ keratinocytes and found an even more significant reduction in proliferative capacity. This cell type contains the population of hyperproliferative keratinocytes in psoriatic epidermis. In conclusion, calcipotriol seems to act via an inhibitory effect on hyperproliferative basal keratinocytes of psoriatic epidermis, rather than via an effect on infiltrating leucocytes, including antigen-presenting cells.
Jensen
A M
AM
Department of Dermatology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Lladó
M B
MB
Skov
L
L
Hansen
E R
ER
Larsen
J K
JK
Baadsgaard
O
O
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003879:Dermatologic Agents / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D007801:Langerhans Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology