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Type of publication: Journal Article
Type of document: Report

Year: 2018

Authors: Shirsath, N; Wagner, K; Tangermann, S; Schlederer, M; Ringel, C; Kenner, L; Brüne, B; Wolf, P

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

Source: Acta Derm-Venereol. 2018; 98(6): 576-584.

Authors Vetmeduni Vienna:

Kenner Lukas
Tangermann Simone

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals

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.

Keywords Pubmed: Aminoquinolines
Disease Models, Animal
Gene Expression Regulationdrug effects
Mice, Inbred BALB C
PUVA Therapy
Photosensitizing Agentspharmacology
Psoriasischemically inducedgeneticsmetabolismprevention & control
Signal Transductiondrug effects
Skindrug effectsmetabolismpathology
Time Factors

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