The monocyte protein C pathway : implications in human diseases

THESIS 7544The protein C (PC) pathway provides an important link between the coagulation, fibrinolytic, and inflammatory pathways. PC/activated protein C (APC) is one o f very few therapies shown to effectively reduce the morbidity and mortality states seen in severe sepsis and septic shock. Originally identified as a naturally occurring anti-coagulant, PC has subsequently been shown to have potent anti-inflammatory properties. Given the significance of activated monocytes in the pathophysiology of severe sepsis and the recent discovery of expression of the endothelial protein C receptor (EPCR) on the monocyte cell surface, we investigated the effect of PC on the gene expression profile of the monocytic cell line THP-1. Microarray technology was used to determine the effect of PC on the expression levels of approximately ten thousand human genes in untreated and LPS activated THP-1 cells. Results were confirmed by investigating the expression of a number of genes included in the microarray by real-time PCR and ELISA