Evaluation of apoptosis regulatory proteins in response to PUVA therapy for psoriasis

Photodermatol Photoimmunol Photomed. 2013 Feb;29(1):18-26. doi: 10.1111/phpp.12012.

Abstract

Background: The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. One of the actions of psoralen ultraviolet A (PUVA) in psoriasis could be exerted through induction of apoptosis of keratinocytes and lymphocytes; however, its exact molecular mechanism is still confusing.

Aim: In this study, we evaluated the expression of pro-apoptotic (P53, Fas and Bax) and anti-apoptotic (Bcl-2) proteins correlating it with apoptotic index (AI) and epidermal thickness in psoriatic skin before and after PUVA therapy.

Methods: Lesional and non-lesional skin biopsy specimens were obtained from 10 patients with generalized plaque psoriasis before and after 8 weeks of PUVA therapy. Histometric measurements of epidermal thickness as well as P53, Fas, Bax and Bcl-2 expressions were evaluated using immunoperoxidase technique and apoptotic cells were detected by terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method.

Results: After PUVA therapy, the epidermal thickness of psoriatic skin was significantly decreased (P < 0.001) and keratinocytes of psoriatic skin showed significant increased expression of P53 (P < 0.001), Fas (P < 0.001) and Bcl-2 (P < 0.001) with no significant change in Bax expression (P > 0.05). Apart from significant decrease of Bcl-2 expression (P = 0.01), no significant difference in all previous markers were encountered in lymphocytes (P53, Fas and Bax; P > 0.05) after PUVA therapy. The AI was significantly increased (P = 0.008) after PUVA therapy especially in lymphocytes (P = 0.002).

Conclusion: The present study suggests that one of the actions of PUVA therapy in psoriasis might be exerted through induction of apoptosis especially of lymphocytes by suppression of Bcl-2 expression and of keratinocytes through P53 and Fas pathways leading to healing of psoriasis.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Apoptosis* / drug effects
  • Apoptosis* / radiation effects
  • Female
  • Gene Expression Regulation* / drug effects
  • Gene Expression Regulation* / radiation effects
  • Humans
  • Keratinocytes* / metabolism
  • Keratinocytes* / pathology
  • Male
  • Middle Aged
  • PUVA Therapy*
  • Psoriasis* / drug therapy
  • Psoriasis* / metabolism
  • Psoriasis* / pathology
  • Time Factors

Substances

  • Apoptosis Regulatory Proteins