Apoptosis, P53 and Bcl-2 expression in response to topical calcipotriol therapy for psoriasis.
BACKGROUND
The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. The P53 and Bcl-2 proteins play a central role in the regulation of apoptosis. This study aimed to evaluate P53 and Bcl-2 expression and apoptotic cells in the psoriatic skin before and after topical calcipotriol therapy.


METHODS
Skin biopsies were obtained from nonlesional and lesional skin of 10 patients with generalized plaque psoriasis before and after treatment with topical calcipotriol ointment. The P53 and Bcl-2 expression was evaluated using immunoperoxidase technique and apoptotic cells by the terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method.


RESULTS
After topical calcipotriol therapy, keratinocytes of psoriatic skin showed significant decrease of P53 (P = 0.002) and increase of Bcl-2 (P = 0.01) expression. On the other hand lymphocytes showed significant decrease of Bcl-2 (P = 0.01). There were no apoptotic cells before treatment but after calcipotriol therapy, apoptosis was more detectable in keratinocytes than in lymphocytes.


CONCLUSIONS
The results of the study suggested that one of the actions of calcipotriol in psoriasis might be exerted through induction of apoptosis, especially of keratinocytes, through a P53-independent pathway. Meanwhile, suppression of Bcl-2 expression in lymphocytes may promote apoptosis of dermal lymphocytes leading to healing of psoriasis.
El-Domyati
Moetaz
M
Department of Dermatology, Al-Minya University Hospital, Al-Minya, Egypt. m_domyati@hotmail.com
Barakat
Manal
M
Abdel-Razek
Rasha
R
El-Din Anbar
Tag
T
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003879:Dermatologic Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D003879:Dermatologic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C055085:calcipotriene; D002117:Calcitriol