Apoptosis, P53 and Bcl-2 expression in response to topical calcipotriol therapy for psoriasis

Int J Dermatol. 2007 May;46(5):468-74. doi: 10.1111/j.1365-4632.2007.03099.x.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / drug effects*
  • Biopsy
  • Calcitriol / analogs & derivatives*
  • Calcitriol / therapeutic use
  • Dermatologic Agents / therapeutic use
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Psoriasis / drug therapy*
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Skin / chemistry
  • Skin / drug effects
  • Skin / pathology
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Dermatologic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • calcipotriene
  • Calcitriol