Psoriasis, a chronic inflammatory immune-mediated disease of skin, is characterized by epidermal hyperplasia and inflammatory infiltrates. Nowadays, there exists a broad spectrum of anti-psoriatic agents, including biologics. Many of these molecules are used to block some cytokines, such as TNF-, IL-12 and IL-23, which are known to be involved in the pathogenesis of this disease. It is known that Notch pathway plays a critical role, not yet well defined, in the pathogenesis of psoriasis. Recently, we have shown a downregulation of Notch-1 expression in skin biopsies from anti-TNF--treated psoriatic patients in comparison to those from patients treated with traditional therapy. In this study, we have extended our earlier observation by including additional components of Notch pathway, such as the Notch ligand Jagged-1 and the Notch effector Hes-1. We have determined, by RT-PCR and immunohistochemistry, the expression levels of Jagged-1 and Hes-1 in skin samples from psoriatic patients undergoing traditional treatments or biologics (Etanercept, a TNFR fusion protein, Adalimumab, a TNF neutralizing antibody, Ustekinumab, a IL-12/IL-23 p40 neutralizing antibody). The expression levels of Jagged-1 were significantly lower in samples from patients undergoing biological therapy in comparison to those from patients treated with traditional therapy. These results support our previous findings which have shown that Notch-1 was downregulated in biologics-treated patients. On the contrary, Hes-1 expression was unchanged. Such a result would be explained by the known Notch-independent activity of Hes. In conclusion, our findings suggest that components of the Notch pathway could be considered as therapeutic targets for the treatment of psoriasis.

Jagged-1/Notch-1/Hes-1 pathway in psoriatic patients: effects of biological therapy

F. D’Amico;MAZZARINO, Maria Clorinda
2014-01-01

Abstract

Psoriasis, a chronic inflammatory immune-mediated disease of skin, is characterized by epidermal hyperplasia and inflammatory infiltrates. Nowadays, there exists a broad spectrum of anti-psoriatic agents, including biologics. Many of these molecules are used to block some cytokines, such as TNF-, IL-12 and IL-23, which are known to be involved in the pathogenesis of this disease. It is known that Notch pathway plays a critical role, not yet well defined, in the pathogenesis of psoriasis. Recently, we have shown a downregulation of Notch-1 expression in skin biopsies from anti-TNF--treated psoriatic patients in comparison to those from patients treated with traditional therapy. In this study, we have extended our earlier observation by including additional components of Notch pathway, such as the Notch ligand Jagged-1 and the Notch effector Hes-1. We have determined, by RT-PCR and immunohistochemistry, the expression levels of Jagged-1 and Hes-1 in skin samples from psoriatic patients undergoing traditional treatments or biologics (Etanercept, a TNFR fusion protein, Adalimumab, a TNF neutralizing antibody, Ustekinumab, a IL-12/IL-23 p40 neutralizing antibody). The expression levels of Jagged-1 were significantly lower in samples from patients undergoing biological therapy in comparison to those from patients treated with traditional therapy. These results support our previous findings which have shown that Notch-1 was downregulated in biologics-treated patients. On the contrary, Hes-1 expression was unchanged. Such a result would be explained by the known Notch-independent activity of Hes. In conclusion, our findings suggest that components of the Notch pathway could be considered as therapeutic targets for the treatment of psoriasis.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/60237
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