Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Shirsath, N; Wagner, K; Roos, S; Schlederer, M; Ringel, C; Kenner, L; Brüne, B; Wolf, P.
8-Methoxypsoralen Plus Ultraviolet A Reduces the Susceptibility of Murine Skin to Mount a Psoriatic Response to Imiquimod Linked with Senescence and Downregulation of Interleukin-9, 17 and Interferon-gamma.
Acta Derm Venereol. 2018; [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Kenner Lukas
Shirsath Nitesh Pralhad
Wagner Karin
Wolf Peter

Dimensions Citations:

Plum Analytics:
The effects of 8-methoxypsoralen plus ultraviolet A (PUVA) and ultraviolet B (UVB) 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 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.

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