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Investigating the effects of IL-36γ on signal transduction in human dermal fibroblasts

Evans, Miles (2019) Investigating the effects of IL-36γ on signal transduction in human dermal fibroblasts. MSc by research thesis, University of York.

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Abstract

Psoriasis is a chronic inflammatory skin condition affecting around 2% of the population. IL-36γ is a member of the IL-1 family of cytokines and has emerged as a pivotal cytokine in psoriasis pathophysiology. The mTOR pathway serves as a key integrator of a wide range of environmental cues, and functions as a central regulator of cellular processes involved with growth and repair. Inhibitors of mTOR have been successfully used in the treatment of several immune mediated conditions, however have been relatively unsuccessful in psoriasis. It has not been studied how mTOR inhibition affects the contribution of stromal cells to psoriasis. We assessed signal transduction downstream of IL-36γ, in primary dermal fibroblasts, with a particular focus on the mTOR axis, and identified a negative role in AKT activation, which could be attributed to feedback loops involved in mTOR signalling. It was demonstrated that NFκB is necessary for cytokine induction by IL-36γ in fibroblasts. We established that mTORC1 negatively regulated cytokine induction, through inhibition with rapamycin. However, we were unable to demonstrate a clear reciprocal effect from the upregulation of mTOR via RNA interference.

Item Type: Thesis (MSc by research)
Academic Units: The University of York > Biology (York)
Depositing User: Mr Miles Evans
Date Deposited: 04 Jun 2019 13:28
Last Modified: 04 Jun 2019 13:28
URI: http://etheses.whiterose.ac.uk/id/eprint/23955

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