The mechanistic target of rapamycin (mTOR) acts through two distinct signalling complexes, known as mTOR complex (mTORC) 1 and mTORC2. One of the main upstream regulator of mTORC1 is tumour necrosis factor (TNF)-α, an important pro-inflammatory cytokine involved in psoriasis. When active, mTORC1 phosphorylates and activates its downstream effector ribosomal protein S6 kinase 1 (S6K1) which is also found increased in psoriasis. Thus, the aim of the study was to assess the involvement of mTORC1 signalling as well as to shed a light on the possible relationship between mTORC1 and TNF-α in psoriasis. Our results showed that mTOR, S6K1 and, in particular, its active form P-S6K1 were increased in psoriatic plaque, suggesting a specific involvement of mTORC1 pathway in the disease. Moreover, for the first time, we reported that PS6K1 was completely abolished after anti-TNF-α therapy, indicating a stronger action of anti-TNF- α agent on mTORC1.

Mechanistic target of rapamycin complex 1 is involved in psoriasis and regulated by anti-TNF-α treatment

BALATO, ANNA;AYALA, FABIO;
2017

Abstract

The mechanistic target of rapamycin (mTOR) acts through two distinct signalling complexes, known as mTOR complex (mTORC) 1 and mTORC2. One of the main upstream regulator of mTORC1 is tumour necrosis factor (TNF)-α, an important pro-inflammatory cytokine involved in psoriasis. When active, mTORC1 phosphorylates and activates its downstream effector ribosomal protein S6 kinase 1 (S6K1) which is also found increased in psoriasis. Thus, the aim of the study was to assess the involvement of mTORC1 signalling as well as to shed a light on the possible relationship between mTORC1 and TNF-α in psoriasis. Our results showed that mTOR, S6K1 and, in particular, its active form P-S6K1 were increased in psoriatic plaque, suggesting a specific involvement of mTORC1 pathway in the disease. Moreover, for the first time, we reported that PS6K1 was completely abolished after anti-TNF-α therapy, indicating a stronger action of anti-TNF- α agent on mTORC1.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11591/453928
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