INDUCTION OF NORMAL AND PSORIATIC PHENOTYPES IN SUBMERGED KERATINOCYTE CULTURES

Lesional psoriatic epidermis displays a number of phenotypic changes t hat are distinct from the differentiation program found in normal inte rfollicular epidermis. In psoriatic epidermis, keratinocytes are hyper proliferative and several differentiation-associated molecules are exp ressed that are absent in normal skin (e.g., cytokeratins (CK) 6, 16, and 17, and the epidermal proteinase inhibitor SKALP/elafin). in addit ion, several molecules which are normally restricted to the stratum gr anulosum are strongly upregulated in the stratum spinosum (e.g., psori asis-associated fatty acid binding protein (PA-FABP), psoriasin, invol ucrin, and transglutaminase). The aim of this study was to develop in vitro culture systems which (a) would allow to study the induction of normal and psoriatic differentiation pathways, and (b) would be amenab le for screening of antipsoriatic drugs. Here we have investigated sev eral models for induction of differentiation with respect to the expre ssion of markers for the normal and psoriatic phenotype. Cell cycle pa rameters and expression levels of CK1, CK10, CK16, SKALP/elafin, trans glutaminase, involucrin, psoriasin, and PA-FABP were assessed in these models using flow cytometry, immunocytochemistry, and Northern blot a nalysis. We observed that induction of differentiation with fetal calf serum resembled the psoriatic phenotype (sustained hyperproliferation ; high levels of CK16, SKALP/elafin, transglutaminase, and involucrin; moderate psoriasin expression), whereas differentiation induced by gr owth factor depletion in a confluent culture resembled the normal diff erentiation phenotype (low proliferative rate; high expression levels of CK1 and CK10; moderate expression of involucrin and transglutaminas e; low expression levels of SKALP/elafin and CK16; absence of psoriasi n). We propose that these models can be used to study expression and p harmacological modulation of selected differentiation genes and the co ordinated expression of sets of genes associated with epidermal differ entiation programs. (C) 1996 Wiley-Liss, Inc.