Project

Profound study of the anti-inflammatory mechanism and therapeutic significance of GILZ in endotocemia ans sepsis.

Duration
01 January 2013 → 31 December 2018
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Humanities
    • Other philosophy, ethics and religious studies not elsewhere classified
    • Other humanities and the arts
Keywords
sepsis GILZ anti-inflammatory mechanism endotocemia
 
Project description

Sepsis is a dondition usally resulting from infection and leading to admission in Intensive Care Units. Sepsis forms a huge unmet medival need since the mortality rate is about 40% and new therapies are not emerging. Glucocorticoids (GCs) are popular anti-inflammatory drugs, but still three major problems are associated with GCs: the anti-inflammatory mechanism is unclear, there are a lot of GC unresponsive patients, and GCs display serious side-effects when used chronically. In sepsis, GCs are suite ineffective. In this project, we address the anti-inflammatory mechanism of GCs and focus thereby on a GC-induced gene product called GILZ. The few data that exist about GILZ suggest that it is a powerful anti-inflammatory molecule. We generated conditional GILZ overexpressing mice and have conditional GILZ-KO mice. The mice will be studied thoroughly in the LPS sepsis model to see whether GILZ is protective, inducible by GCs but also by anti-inflammatory IL-10. Our preliminary data show that in acute inflammation GILZ is downregulated fastly. We will study how come and how to prevent this. Also, we will develop and study GILZ therapeutic tools. Finally, since sepsis is characterized by an early GC therapy is so ineffective in sepsis. We will study if GILZ mediates the immune-suppressive ohase of sepsis, and whether inhibition of GILZ is the way to go in the late phase of bacterial sepsis.