Defect of epidermal 12(S)-hydroxyeicosatetraenoic acid receptors in psoriasis.
12-hydroxyeicosatetraenoic acid (12-HETE) is assumed to play a central role in the pathophysiology of psoriasis. Since its effects in skin are mediated by specific high-affinity receptors, we studied the receptor characteristics in cultured epidermal cells from involved and apparently healthy skin of psoriasis patients by radioligand binding assay. Involved and uninvolved psoriatic epidermal cells showed a fourfold decrease in the number of 12-HETE binding sites as compared with normal healthy individuals and patients with atopic dermatitis, while receptor affinity remained unchanged. The decrease in receptor number was evident in psoriatic cells even in long-term culture and was not due to receptor down-regulation, defective response to interferon gamma or to protease degradation of receptor protein. The decrease in the number of 12-HETE receptors detectable even in clinically normal psoriatic skin functionally leads to diminished 12-HETE uptake and may thus represent a primary central molecular defect in the pathophysiology of the disease.
Arenberger
P
P
Department of Dermatology, University of Munich, Germany.
Kemény
L
L
Ruzicka
T
T
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018055:Receptors, Eicosanoid; D014357:Trypsin / Q000494:pharmacology
C066652:12-hydroxyeicosatetraenoic acid receptor; D006893:Hydroxyeicosatetraenoic Acids; D011956:Receptors, Cell Surface; D018055:Receptors, Eicosanoid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D007371:Interferon-gamma; D014357:Trypsin