Grant: Operating Grant

Although macrophage activation is an important step in both innate and acquired immune responses, this inflammatory reaction must be carefully regulated in order to avoid pathological consequences. One cytokine, soluble proteins which cells use to communicate and regulate each other, called interleukin-10 (IL10) is a key regulator of macrophage activation. Studies directed at understanding the mechanism by which IL10 inhibits macrophage activation have focused on examining whether IL10 alters intracellular signalling pathways shown to be essential for the function of macrophage activators. Several studies, for example, have shown that IL10 inhibits the NFkB and the Map kinase pathways involve inLPS activation of macrophages. However, the significance of these observation remain unclear because of the variability of the results and because it has not been possible to link them mechanistically to any IL10 signalling pathway. To approach this problem from a different perspective, my studies will concentrate on characterizing IL10-induced signalling pathways and the role they play in mediating IL10's anti-inflammatory action. An understanding of how IL10 deactivates macrophages may provide new insights into development of anti-inflammatory drugs or therapies.