Effects of 1 alpha,25-dihydroxy-vitamin D3 and calcipotriol on organotypic cultures of outer root sheath cells: a potential model to evaluate antipsoriatic drugs.
In the human hair follicle, outer root sheath (ORS) cells constitutively express the hyperproliferation-associated keratins 6, 16 and 17 instead of keratins 1 and 10 found in interfollicular epidermis. In organotypic cultures. ORS cells form a stratified epithelium which in many respects resembles psoriatic skin: it has a hyperplastic tissue architecture and a poorly developed granular layer, and expresses hyperproliferation-associated keratins. Therefore, we studied the effects of the antipsoriatic compounds 1 alpha,25-dihydroxy-vitamin D3 (1 alpha,25-(OH)2-D3) and its synthetic derivative calcipotriol on cultured ORS cells. In monolayer cultures, 10(-6) M 1 alpha,25-(OH)2-D3 or calcipotriol completely blocked ORS cell proliferation. This inhibitory effect was substantially reduced at 10(-8) M. Incubation of organotypic ORS cultures with both vitamin D analogues resulted in a marked thinning of the living cell compartment concomitant with a thickening of the horny layer. A reduced expression of differentiation markers such as keratins 10, 16 and 17, involucrin and filaggrin paralleled the thinning of the stratum Malpighi. As determined by quantification of BrdU-positive cells, ORS cell proliferation was apparently not affected by the vitamin D analogues, indicating that these compounds mainly operate by accelerating the differentiation pathway within the suprabasal living cell compartment. No alteration in the expression of the alpha 6- and beta 1-integrin chains was found.
Limat
A
A
Universitäts-Hautklinik, Inselspital, Bern, Switzerland.
Hunziker
T
T
Braathen
L R
LR
D000328:Adult; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003879:Dermatologic Agents / Q000494:pharmacology*; D000091344:Filaggrin Proteins; D006197:Hair / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D008954:Models, Biological; D009924:Organ Culture Techniques; D011565:Psoriasis / Q000188:drug therapy*
D003879:Dermatologic Agents; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C055085:calcipotriene; D007633:Keratins; D002117:Calcitriol