Proliferation and glycosaminoglycans secretion in fibroblasts from psoriatic skin: differential responses to retinoids.
The effects of four retinoids, all-trans-retinoic acid (tretinoin), 13-cis-retinoic acid (isotretinoin), R0 10-1670 (etretin) and the arotinoid, R0 15-0778, on fibroblast proliferation and glycosaminoglycans (GAG) secretion in vitro were studied. Fibroblasts 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 greater than isotretinoin greater than etretin greater than 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 greater than etretin greater than isotretinoin greater than tretinoin. Electrophoresis of [3H]-labelled glycosaminoglycans secreted in the presence of 10(-7) M 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.
D017255:Acitretin; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D015474:Isotretinoin; D011565:Psoriasis / Q000378:metabolism / Q000503:physiopathology*; D012176:Retinoids / Q000494:pharmacology; D012867:Skin / Q000378:metabolism / Q000503:physiopathology*; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology*
D006025:Glycosaminoglycans; D012176:Retinoids; D014212:Tretinoin; C053595:temarotene; D015474:Isotretinoin; D017255:Acitretin