Activator protein 1 DNA binding activity is decreased in lesional psoriatic skin compared with nonlesional psoriatic skin.
BACKGROUND
Psoriasis is a common benign skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes. The transcription factor activator protein 1 (AP-1) is known to play an important role in cell proliferation and differentiation.


OBJECTIVE
To investigate AP-1 DNA binding activity in psoriatic skin.


METHODS
Keratome biopsies were taken from patients with plaque-type psoriasis. Electrophoretic mobility shift assays were used to determine the AP-1 DNA binding activity, whereas Western and Northern blotting was used to determine Jun and Fos protein and mRNA expression.


RESULTS
We found that AP-1 DNA binding activity was almost completely abolished in lesional psoriatic skin compared with nonlesional psoriatic skin. Furthermore, experiments revealed that the protein and mRNA expression of the AP-1 subunits c-Fos, Fra-1 and c-Jun was reduced in lesional psoriatic skin compared with nonlesional psoriatic skin, whereas the protein and mRNA expression of the subunit JunB was increased. Topical application of the vitamin D analogue calcipotriol under occlusion to involved psoriatic skin for 4 days resulted in an increase in AP-1 DNA binding activity, and an increase in the protein and mRNA expression of c-Fos, Fra-1 and c-Jun, together with a decrease in JunB protein and mRNA expression.


CONCLUSIONS
Together, these results suggest that the activity of the transcription factor AP-1 is impaired in lesional psoriatic skin and that this impairment may be important for the disturbed epidermal growth observed in psoriasis.
Johansen
C
C
Department of Dermatology, Marselisborg Hospital, University of Aarhus, P.P.Orumsgade 11, DK-8000 Aarhus C, Denmark. clausoglotte@hotmail.com
Kragballe
K
K
Rasmussen
M
M
Dam
T N
TN
Iversen
L
L
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D015153:Blotting, Western; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D003879:Dermatologic Agents / Q000627:therapeutic use; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism*
D004268:DNA-Binding Proteins; D003879:Dermatologic Agents; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C055085:calcipotriene; D002117:Calcitriol