Study on the impact of Toll-like Receptor 4 (TLR4) modulation in rare inflammatory-fibrotic diseases

The project focuses on the modulation of fibrotic phenotype up-set in rare diseases through a Toll-like Receptor 4 (TLR4) antagonist. In particular, in this work, we started to test the possible impact on fibrosis progression of FP7 and FP12 that showed inhibition activity against TRL4 activation by LPS in a dose-dependent way in both human and murine cells 1. Fibrosis is an outcome of the repair response to tissue damage caused by inflammation. When the fibrotic process is excessive or dysregulated it leads to a pathological condition that can affect different organs and functions. Here, it is now clear that inflammation, which however is not the only trigger, plays a key role in the critical cellular process of fibroblast activation that leads to fibrosis up-set 2. The recent discovery of complex crosstalk between fibrosis progression and inflammatory pathways underlines the central role of TRL4 and its potential as a new drug target3. Here it is proposed an in vitro screening on cellular models of fibrosis with TLR4 antagonists to identify new potential drugs targeting Idiopathic Pulmonary Fibrosis (IPF), a rare fibrotic pathology where a pivotal role of TLR4-mediated inflammation has been observed 4 5.