Psoriasis is a chronic inflammatory skin disease that affects 2-3% of the Western population. The aim of this thesis was to illuminate the molecular effects of narrow-band (NB-) UVB phototherapy, a highly effective systemic treatment modality in psoriasis, in order to clarify the mechanism of the resolution of psoriatic skin inflammation and the immune pathogenesis of the disease. In addition, by identification of pathways that are responsible for the effectiveness of NB-UVB we aimed for detecting novel potential therapeutic target molecules for the treatment of psoriasis. Epidermal gene expression profiles were analyzed of patients with psoriasis undergoing standard NB-UVB phototherapy before, during and after the therapy both from lesional and non-lesional skin. The results were validated using primary human keratinocytes, cultured human skin biopsies, and the imiquimod-induced psoriasis-like mouse model. In a separate study, cellular and molecular effects of NB-UVB were compared with those of the 585 nm pulsed dye laser that selectively destroyes blood vessels. We have shown that NB-UVB therapy affects 1) signal transducer and activator of transcription (STAT) 3 and the T helper 17 pathway which in the epidermis is represented by antimicrobial peptides; 2) the interferon-induced innate double-stranded RNA receptors melanoma differentiation associated gene (MDA) 5 and retinoic acid-inducible gene (RIG)-I, and 3) the transcription factor GATA3 with involvement in the proliferation and differentiation of epidermal keratinocytes. Our findings indicate that these molecules and pathways are critical in the pathophysiology of psoriasis and might represent novel therapeutic targets. Further studies need to investigate the possibilities of specifically modulate these molecules and to determine their usefulness as therapeutic targets in psoriasis.

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J.D. Laman (Jon) , E.P. Prens (Errol)
Erasmus University Rotterdam
hdl.handle.net/1765/17265
Erasmus MC: University Medical Center Rotterdam

Rácz, E. (2009, November 19). Molecular targets of Narrow-Band UVB Phototherapy in Psoriasis. Retrieved from http://hdl.handle.net/1765/17265