Effective Treatment of Psoriasis with Narrow-Band UVB Phototherapy Is Linked to Suppression of the IFN and Th17 Pathways
| Autor: | Wilfred F. J. van IJcken, Frank J. T. Staal, Marius Kant, Jon D. Laman, Emőke Rácz, Ewout M. Baerveldt, Sabine Mourits, Dick de Ridder, Errol P. Prens, Leslie van der Fits, Dorota Kurek, Zeliha Ozgur |
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| Přispěvatelé: | Dermatology, Cell biology, Immunology |
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Cellular differentiation Dermatology Biology Antibodies Monoclonal Humanized Ultraviolet therapy Biochemistry Downregulation and upregulation Psoriasis Ustekinumab medicine Humans STAT3 Molecular Biology Aged integumentary system Gene Expression Profiling Antibodies Monoclonal Cell Differentiation Cell Biology Middle Aged medicine.disease Immunology STAT protein biology.protein Cancer research Th17 Cells Female Ultraviolet Therapy Interferons Epidermis Signal transduction Signal Transduction medicine.drug |
| Zdroj: | Journal of Investigative Dermatology, 131(7), 1547-1558. Nature Publishing Group |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2011.53 |
| Popis: | Narrow-band ultraviolet-B (NB-UVB) phototherapy is an effective treatment for psoriasis. The molecular mechanisms underlying its efficacy are incompletely understood. To identify NB-UVB-induced molecular pathways that may account for its anti-inflammatory efficacy, gene expression profiling was performed using epidermal RNA from lesional and nonlesional skin from patients with psoriasis undergoing NB-UVB therapy. Downregulation of Th17 signaling pathway was observed during NB-UVB therapy in psoriatic epidermis. Strong inhibition of the Th17 pathway by UVB was confirmed in an ex vivo organ culture system by demonstrating reduced signal transducer and activator of transcription 3 (STAT3) phosphorylation and beta-defensin-2 production. These results were further substantiated by demonstrating that NB-UVB inhibited the Th17-dependent psoriasis-like dermatitis in mice. Other pathways affected by NB-UVB therapy include the IFN signaling pathway, epidermal differentiation, and other well-known therapeutic targets in psoriasis, such as the glucocorticoid, vitamin D, peroxisome proliferator-activated receptor, and IL-4 signaling pathways. In conclusion, clinical improvement of psoriasis by NB-UVB is linked to suppression of Th17 and type I and type II IFN signaling pathways, which are critical in the pathogenesis of the disease. Our results show that clinically effective NB-UVB therapy is based on suppression of a broad range of important molecular pathways in psoriatic skin. |
| Databáze: | OpenAIRE |
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