Proliferation and glycosaminoglycans secretion in fibroblasts from psoriatic skin: differential responses to retinoids

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Abstract
The effects of four retinoids, all-trans-retinoic acid (tretinoin), 13-cis-retinoic acid (isotretinoin), Ro 10-1670 (etretin) and the arotinoid, Ro 15-0778, on fibroblast proliferation and glycosaminoglycans (GAG) secretion in vitro were studied. Fibroblast lines cultured from normal skin (HSF) were compared with those from lesional (PSA) and non-lesional (PSB) psoriatic skin. In general, the retinoids inhibited proliferation; the action was cytostatic, in rank order tretinoin > isotretinoin > etretin > arotinoid. The psoriatic cells tended to be more sensitive than the HSF lines, overall mean proliferation values (.+-. SEM), as a percentage of untreated controls being: HSF 72 .+-. 3, PSA 61 .+-. 3 and PSB 54 .+-. 3. Stimulation of GAG secretion at low concentrations (10-7 M) of all four retinoids, declined as concentrations increased, and secretion was inhibited at 10-4 M in PSB fibroblasts. Calculation of effects on GAG secretion due to changes in cell density confirmed the rank order for direct stimulation of secretion as arotinoid > etretin > isotretinoin < tretinoin. Electrophoresis of [3H]-labelled glycosaminoglycans secreted in the presence of 10-7M arotinoid showed that it was predominantly hyaluronic acid, as in untreated cells. These data confirm that different retinoids have contrasting levels of effects on mesenchymal cells and suggest a greater sensitivity to drugs in fibroblasts from psoriatic skin.