8-Methoxypsoralen Plus Ultraviolet A Reduces the Psoriatic Response to Imiquimod in a Murine Model

Acta Derm Venereol. 2018 Jun 8;98(6):576-584. doi: 10.2340/00015555-2905.

Abstract

The effects of 8-Methoxypsoralen plus ultraviolet A (PUVA) or ultraviolet B (UVB) alone on imiquimod-induced psoriasis were examined in a mouse model. Mouse skin was treated with repetitive sub-phototoxic doses of PUVA or UVB before or during the induction of toll-like receptor 7/8 activation and psoriasis through the application of imiquimod. PUVA, to a greater degree than UVB, suppressed the established imiquimod-induced psoriatic phenotype, but pretreatment with PUVA prior to administration of imiquimod also reduced the susceptibility of murine skin to respond to imiquimod to a greater degree than did pretreatment with UVB. PUVA downregulated baseline levels of miRNA27a and 29a, as well as interferon-γ, interleukin-17 and -9, cytokines, which drive psoriatic inflammation. Microarray analysis showed enrichment of senescence pathway genes linked to upregulation of p16/p21 proteins after PUVA pretreatment. However, the anti-psoriatic effect of PUVA was lost when there was an interval of 7 days between final exposure to PUVA and the start of administration of imiquimod. This indicated that (UVB and) PUVA diminished imiquimod-induced established psoriatic inflammation, but also primed the skin in favour of a reduced responsiveness to toll-like receptor activation.

MeSH terms

  • Aminoquinolines*
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation / drug effects
  • Imiquimod
  • Methoxsalen / pharmacology*
  • Mice, Inbred BALB C
  • PUVA Therapy*
  • Photosensitizing Agents / pharmacology*
  • Psoriasis / chemically induced
  • Psoriasis / genetics
  • Psoriasis / metabolism
  • Psoriasis / prevention & control*
  • Signal Transduction / drug effects
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Time Factors

Substances

  • Aminoquinolines
  • Cytokines
  • Photosensitizing Agents
  • Imiquimod
  • Methoxsalen