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Activator protein 1 DNA binding activity is decreased in lesional psoriatic skin compared with nonlesional psoriatic skin
Author(s) -
Johansen C.,
Kragballe K.,
Rasmussen M.,
Dam T.N.,
Iversen L.
Publication year - 2004
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2004.06088.x
Subject(s) - psoriasis , junb , messenger rna , activator (genetics) , microbiology and biotechnology , calcipotriol , biology , transcription factor , cancer research , endocrinology , medicine , immunology , gene , receptor , biochemistry
Summary 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. Objectives 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.