ALA-PDT alleviates the psoriasis by inhibiting JAK signalling pathway

Exp Dermatol. 2019 Nov;28(11):1227-1236. doi: 10.1111/exd.14017. Epub 2019 Oct 23.

Abstract

Background: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a well-known treatment for non-hypertrophic actinic keratoses and superficial basal-cell carcinomas.

Objectives: In this study, we first revealed that ALA-PDT treatment effectively ameliorated the psoriasis-like lesion in imiquimod (IMQ)-induced mouse model and further explored the potential molecular mechanism and related signalling pathways during the treatment. Besides, we also confirmed a significant alleviation of ALA-PDT therapy on IFN-γ-induced over-proliferation of keratinocytes.

Methods: H&E staining was conducted to reveal the histological changes of mice in different groups. The different expression levels of RNA were illustrated by using QRT-PCR. Western blot was performed to confirm the various expression levels of protein in mice. In vitro, cell proliferation and cell cycle were evaluated by cell counting kit-8 and flow cytometry assay, respectively.

Results: The result showed that ALA-PDT's anti-proliferation effect and regulation on Socs1/3, JAK1/2 and K17 in IFN-γ-induced keratinocytes were largely weakened by NAC, indicating that ALA-PDT attenuated the proliferation of IFN-γ-induced keratinocytes by enhancing ROS level.

Conclusions: These results demonstrated that ALA-PDT largely activated the productivity of Socs1/3 in a ROS-dependent manner. Socs1/3 is a potential blocker in JAK signalling pathway and inhibits the proliferation and keratinization of keratinocytes in psoriasis.

Keywords: JAK pathway; Photodynamic therapy; keratinocytes; reactive oxygen species.

MeSH terms

  • Aminolevulinic Acid / pharmacology*
  • Animals
  • Drug Evaluation, Preclinical
  • Female
  • Imiquimod
  • Interferon-gamma
  • Janus Kinases / metabolism*
  • Keratinocytes / drug effects
  • Mice, Inbred BALB C
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*
  • Psoriasis / drug therapy*
  • Psoriasis / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Suppressor of Cytokine Signaling Proteins / metabolism

Substances

  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Suppressor of Cytokine Signaling Proteins
  • Interferon-gamma
  • Aminolevulinic Acid
  • Janus Kinases
  • Imiquimod