Induction of normal and psoriatic phenotypes in submerged keratinocyte cultures

F Van Ruissen, GJ De Jongh… - Journal of cellular …, 1996 - Wiley Online Library
F Van Ruissen, GJ De Jongh, PLJM Zeeuwen, PEJ Van Erp, P Madsen, J Schalkwijk
Journal of cellular physiology, 1996Wiley Online Library
Lesional psoriatic epidermis displays a number of phenotypic changes that are distinct from
the differentiation program found in normal interfollicular epidermis. In psoriatic epidermis,
keratinocytes are hyperproliferative and several differentiation‐associated molecules are
expressed that are absent in normal skin (eg, cytokeratins (CK) 6, 16, and 17, and the
epidermal proteinase inhibitor SKALP/elafin). In addition, several molecules which are
normally restricted to the stratum granulosum are strongly upregulated in the stratum …
Abstract
Lesional psoriatic epidermis displays a number of phenotypic changes that are distinct from the differentiation program found in normal interfollicular epidermis. In psoriatic epidermis, keratinocytes are hyperproliferative and several differentiation‐associated molecules are expressed that are absent in normal skin (e.g., cytokeratins (CK) 6, 16, and 17, and the epidermal proteinase inhibitor SKALP/elafin). In addition, several molecules which are normally restricted to the stratum granulosum are strongly upregulated in the stratum spinosum (e.g., psoriasis‐associated fatty acid binding protein (PA‐FABP), psoriasin, involucrin, 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 amenable for screening of antipsoriatic drugs. Here we have investigated several models for induction of differentiation with respect to the expression of markers for the normal and psoriatic phenotype. Cell cycle parameters and expression levels of CK1, CK10, CK16, SKALP/elafin, transglutaminase, involucrin, psoriasin, and PA‐FABP were assessed in these models using flow cytometry, immunocytochemistry, and Northern blot analysis. 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 growth factor depletion in a confluent culture resembled the normal differentiation phenotype (low proliferative rate; high expression levels of CK1 and CK10; moderate expression of involucrin and transglutaminase; low expression levels of SKALP/elafin and CK16; absence of psoriasin). We propose that these models can be used to study expression and pharmacological modulation of selected differentiation genes and the coordinated expression of sets of genes associated with epidermal differentiation programs. © 1996 Wiley‐Liss, Inc.
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