Control of inflammation via the phosphorylation of tristetraprolin (TTP)

Inflammation is normally a short-lived and beneficial response to infection or injury. However, in diseases like rheumatoid arthritis, inflammation persists in the absence of infection or injury, causing pain, disfunction and disfigurement. It is possible that persistent inflammation is due to the failure of resolution mechanisms, which would normally help to terminate an inflammatory response. In this project we are exploring the idea of stimulating or reactivating one of the body s natural inflammatory off-switches in order to treat chronic inflammatory diseases.

This project will investigate the impact of signalling pathways on the expression and function of the mRNA destabilising protein tristetraprolin (TTP), a negative regulator of inflammatory mediator gene expression. We will investigate the hypothesis that TTP is present at sites of chronic inflammation but inactivated by phosphorylation. We will examine the feasibility of reactivating latent TTP as a novel anti-inflammatory strategy.