EGF receptor expression and growth of psoriatic and normal human keratinocytes are modulated by 1.25 (OH)2-vitamin D3 ex vivo.
Calcitriol or 1.25 (OH)2-vitamin D3 is used in the treatment of psoriasis as an inhibitor of cell proliferation. We studied the action of calcitriol ex vivo on the growth of psoriatic and normal human keratinocytes, and on the expression of the EGF receptor. Third passaged normal and psoriatic keratinocytes were seeded (10(4)/cm2) in 24-well dishes in serum-free medium (MCDB supplemented with amino acids, with either 0.1 or 1.1 mM of calcium) and 10(-9) M calcitriol. When subconfluence was reached, cell counts and 125I-EGF binding studies were performed. Cell counts showed at least a 50% decrease in growth under all conditions studied (normal or psoriatic keratinocytes; 0.1 or 1.1 mM calcium) when calcitriol was added. 125I-EGF binding studies showed a decrease in total receptor numbers in the presence of calcitriol with acceleration of binding at low concentrations of 125I-EGF. Scatchard plot analysis showed only one type of high affinity receptor. Receptor sites were decreased (30% to 40% of controls) in the presence of calcitriol together with a decrease in the dissociation constant. In conclusion, at almost physiological concentrations ex vivo, calcitriol strongly decreased normal and psoriatic keratinocyte growth. This potent antiproliferative effect could in part be explained by the capacity of calcitriol to downregulate EGF receptor expression.
Boisseau-Garsaud
A M
AM
Laboratoire de Dermatologie, Université de Bordeaux II, France.
Donatien
P
P
Margerin
C
C
Taïeb
A
A
D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D002117:Calcitriol; D002118:Calcium