Pharmacological inhibition of macrophage activation
Macrophages are innate immune cells that specialise in sensing and responding to the presence of pathogens and they have been causally involved in the pathogenesis of both sepsis and rheumatoid arthritis (RA). Both diseases represent a high cost to the economy and society of European countries characterized by an aging population as well as developing countries. Sepsis is the first cause of death in hospitalized patient, with an estimate of 5 million deaths each year. Currently, there are no effective treatment protocols or strategies to deal with sepsis and several approaches targeting known cellular
pathways have failed. RA is a chronic condition that affects 1% of the population worldwide. Despite the existence of established guidelines, 66% of patient inadequately respond to the therapy. Our group discovered that DNA damage is involved in the control of macrophages activation, unveiling a novel and untapped pathway potentially ripe for new approaches to modulate their activity. Thus, our proposed project is to test drugs targeting factors involved in DNA metabolism to treat inflammatory immune disease. Our plan involves a first part using an in vitro strategy to test the efficacy of the inhibitors on different macrophages cell lines and a second part involving the use of well-established animal disease models.