Psoralen with ultraviolet A-induced apoptosis of cutaneous lymphoma cell lines is augmented by type I interferons via the JAK1–STAT1 pathway

Walter Joseph Liszewski, David Gram Naym, Edyta Biskup, Robert Gniadecki*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Background: Photochemotherapy with psoralen and ultraviolet A (PUVA), with or without adjuvant interferon-α (IFN-α), is a first-line therapy for early-stage mycosis fungoides and other forms of cutaneous T-cell lymphoma (CTCL). However, the mechanism by which PUVA with IFN-α work in CTCL is poorly understood. Purpose: To develop a model to investigate the mechanisms of PUVA and PUVA with IFN-α in CTCL cells. Methods: An in vitro model to study the molecular mechanisms of PUVA was created using two different CTCL cell lines, MyLa, which has functional p53, and HuT-78, in which p53 is inactivated due to a homozygous nonsense mutation. Results: PUVA caused G2/M cell cycle block and apoptosis of MyLa and HuT-78 accompanied by increase in the expression of the mitochondrial pro-apoptotic genes Bax, BAK, and PUMA and a downregulation in anti-apoptotic Bcl-2. p53 was induced and c-Myc was repressed by PUVA, but neither were essential for PUVA-induced apoptosis. IFN-α augmented PUVA-induced apoptosis via the JAK1 pathway, and this activity could be inhibited by ruxolitinib. Conclusion: PUVA induces p53-independent apoptosis in CTCL cell lines, and this process is augmented by type I interferons via the JAK1 pathway.

Original languageEnglish (US)
Pages (from-to)164-171
Number of pages8
JournalPhotodermatology Photoimmunology and Photomedicine
Volume33
Issue number3
DOIs
StatePublished - May 1 2017

Keywords

  • apoptosis
  • cutaneous lymphoma
  • interferons
  • JAK
  • psoralen with ultraviolet A

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Radiology Nuclear Medicine and imaging
  • Dermatology

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