Proliferation and interferon-gamma receptor expression in psoriatic and healthy keratinocytes are influenced by interactions between keratinocytes and fibroblasts in a skin equivalent model.
Epidermal-dermal interactions were studied in a skin equivalent model. Six combinations of keratinocytes and fibroblasts from healthy and psoriatic skin were used. TPA (12-O-tetradecanoylphorbol-13-acetate) was used to determine whether the expression of the IFN-gamma receptors in keratinocytes was related to epidermal differentiation and proliferation. These phenomena were assessed by immunohistochemistry. In all epidermal outgrowths, the epidermal growth factor receptor was expressed throughout the epidermis, cytokeratin 16 suprabasally, and filaggrin and involucrin in its superficial part. The IFN-gamma receptor was expressed throughout the epidermis, but was unevenly distributed. The expression of the IFN-gamma receptor was quantified by confocal laser scanning microscopy both in the whole of epidermis and in areas with the strongest intensity. The total amount varied to a minor degree in the epidermal outgrowths of different origins and was unaffected by TPA. In high-intensity areas interactions between keratinocytes and fibroblasts did influence the amount of IFN-gamma receptor expression and TPA decreased the expression by 13%. There was no correlation between the proliferation rate and the expression of the IFN-gamma receptor. Psoriatic and healthy keratinocytes were equally well differentiated in the skin equivalents. The interferon-gamma receptor was similarly expressed under these conditions. The growth rate, assessed by Ki-67-positive nuclei in the basal layer, was highest in healthy keratinocytes. Keratinocytes from psoriatic lesions increased their growth rate when cocultured with psoriatic fibroblasts compared with normal ones, indicating that fibroblasts may be of importance for epidermal hyperproliferation in psoriatic lesions.
D000328:Adult; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000091344:Filaggrin Proteins; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D017471:Receptors, Interferon / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006684:HLA-DR Antigens; D017471:Receptors, Interferon; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate