Keratin gene expression during the resolution of psoriatic plaques: effect of dithranol, PUVA, etretinate and hydroxyurea regimens.
Quantitative changes in the levels of keratin polypeptides extracted from keratotome shavings from psoriatic epidermis were measured by using one-dimensional SDS-PAGE, followed by scanning densitometry. Values obtained were compared with results for non-lesional epidermis and from epidermis from normal individuals. Patients on four different treatment regimens were investigated by repeated sampling over 3-4 months starting before therapy commenced. The levels of four keratins changed significantly: keratins I (70 kd) and 2 (66 kd) tended to rise to normal levels, while keratins 16 (50 kd) and 18 (44 kd) fell to normal levels. There were differential effects as well as differences in the rates of normalization depending upon the treatment regimen. The most rapid normalization of the levels of all four keratins was observed with topical dithranol (anthralin) treatment (five patients) with plaque resolution and keratin level normalization after 7-9 weeks. Oral hydroxyurea (three patients) had similar effects, but over a longer time scale (20 weeks). In contrast, oral etretinate (four patients) caused a normalization of all except keratin 2 (66 kd) over a period of 20-28 weeks, and keratin I (70 kd) levels tended to 'overshoot' the normal level. PUVA (five patients) caused rapid normalization (in 9-12 weeks) of keratins 2 (66 kd) and 18 (44 kd), but had much weaker effects on keratins I (70 kd) and 10 (57 kd). These results suggest that resolution of lesions as judged by clinical criteria can occur without normalization of the keratin electrophoretic profile. Possibly the most reliable marker of clinical resolution was the reduction in keratin 16 (50 kd), since treatment effects on the differentiation of keratins I (70 kd) and 2 (66 kd) were different.
Holland
D B
DB
Department of Dermatology, General Infirmary, Leeds, U.K.
Wood
E J
EJ
Cunliffe
W J
WJ
Turner
D M
DM
D000875:Anthralin / Q000627:therapeutic use; D003720:Densitometry; D004586:Electrophoresis; D004817:Epidermis / Q000378:metabolism; D005050:Etretinate / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D015151:Immunoblotting; D007633:Keratins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D011701:PUVA Therapy; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D005050:Etretinate; D007633:Keratins; D000875:Anthralin; D006918:Hydroxyurea