Cultured psoriatic fibroblasts from involved and uninvolved sites have a partial but not absolute resistance to the proliferation-inhibition activity of 1,25-dihydroxyvitamin D3.
We examined the responsiveness of cultured dermal fibroblasts from biopsies of uninvolved and involved areas of skin from six patients with psoriasis to the cell-proliferation-inhibition activity of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3). Cultured fibroblasts from age-matched controls responded to 1,25-(OH)2-D3 (at 0.01, 1, 10, and 100 microM) in a dose-dependent fashion, whereas cultured psoriatic fibroblasts from involved or uninvolved skin showed no inhibition of proliferation when exposed to 0.01 or 1 microM of 1,25-(OH)2-D3. However, 1,25-(OH)2-D3 did inhibit proliferation of cultured psoriatic fibroblasts when the concentrations were increased to 10 and 100 microM. An analysis of the 1,25-(OH)2-D3 receptors in cultured psoriatic fibroblasts from uninvolved skin revealed that the Kd, nmax, and sedimentation coefficient were identical to the receptors found in the fibroblasts from age-matched controls. Therefore, cultured psoriatic fibroblasts from involved and uninvolved skin have a partial resistance to 1,25-(OH)2-D3, suggesting that there may be a biochemical defect that is inherent in the dermal fibroblasts of psoriatic patients. Recognition of this defect may provide a new approach for the evaluation of the cause and treatment of this disfiguring skin disorder.
MacLaughlin
J A
JA
Gange
W
W
Taylor
D
D
Smith
E
E
Holick
M F
MF
D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004351:Drug Resistance; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007700:Kinetics; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology*; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000473:pathology*
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol