Effect of calcitriol on growth, differentiation, chemokine mRNA expression of cultured keratinocytes and on keratinocyte-T cell binding.
Calcitriol has recently been shown to be effective against psoriasis. However, its mode of action is not exactly known. The present study focused on the influence of calcitriol on growth, differentiation, chemokine mRNA and ICAM-1 mRNA expression of keratinocytes (KC) and on the binding of T-cells to keratinocytes. In vitro studies showed that calcitriol has a strong anti-proliferative effect and induces terminal differentiation. gamma-IP-10 and ICAM-1 mRNA were induced by gamma-IFN, an induction not influenced by calcitriol. Moreover, the functional expression of ICAM-1 on the KC cell surface as measured by a cell adhesion assay, was not influenced either. IL-8 and huGRO mRNAs were constitutively produced in KC, as was demonstrated after incubation with cycloheximide. Up-regulation of both IL-8 and huGRO mRNA by IL-1 alpha was also not affected by calcitriol. It is concluded that calcitriol has a strong antiproliferative activity and does not interfere with KC responsiveness to gamma-IFN and IL-alpha induced chemokine expression or with the adhesion of T-cells to keratinocytes.
de Haan
P
P
Department of Dermatology, Free University Hospital, Amsterdam, The Netherlands.
Sampat
S
S
van der Raaij
E M
EM
Bruynzeel
I
I
Boorsma
D M
DM
Willemze
R
R
Stoof
T J
TJ
D002117:Calcitriol / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*
D002630:Chemotactic Factors; D016207:Cytokines; D012333:RNA, Messenger; D002117:Calcitriol