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 constitutive ly express the hyperproliferation-associated keratins 6, 16 and 17 ins tead of keratins 1 and 10 found in interfollicular epidermis. In organ otypic cultures, ORS cells form a stratified epithelium which in many respects resembles psoriatic skin: it has a hyperplastic tissue archit ecture and a poorly developed granular layer, and expresses hyperproli feration-associated keratins. Therefore, we studied the effects of the antipsoriatic compounds 1alpha,25-dihydroxy-vitamin D3 (1alpha,25-(OH )2-D3) and its synthetic derivative calcipotriol on cultured ORS cells . In monolayer cultures, 10(-6) M 1alpha,25-(OH)2-D3 or calcipotriol c ompletely blocked ORS cell proliferation. This inhibitory effect was s ubstantially reduced at 10(-8) M. Incubation of organotypic ORS cultur es with both vitamin D analogues resulted in a marked thinning of the living cell compartment concomitant with a thickening of the horny lay er. A reduced expression of differentiation markers such as keratins 1 0, 16 and 17, involucrin and filaggrin paralleled the thinning of the stratum Malpighi. As determined by quantification of BrdU-positive cel ls, ORS cell proliferation was apparently not affected by the vitamin D analogues, indicating that these compounds mainly operate by acceler ating the differentiation pathway within the suprabasal living cell co mpartment. No alteration in the expression of the alpha6- and beta1-in tegrin chains was found.