PhD ceremony Ms. A.M.T. Schippers: Actors in a dynamic scene. On the interplay between macrophages and local mediators in the fibrotic liver
|Mo 29-04-2013 at 14:30
PhD ceremony: Ms. A.M.T. Schippers, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen
Dissertation: Actors in a dynamic scene. On the interplay between macrophages and local mediators in the fibrotic liver
Promotor(s): prof. K. Poelstra
Faculty: Mathematics and Natural Sciences
The research of Marlies Schippers has provided new insights into the complex process of fibrogenesis which is very important for the development of a therapy for this serious disease.
During liver injury by for instance toxins, autoimmune diseases, or genetic disorders, damaged hepatocytes secrete various mediators that activate other hepatic cells. While a short, inflammatory response is beneficial to restore liver architecture, uncontrolled continuation of this process may lead to liver fibrosis. Liver fibrosis is characterized by an abundant deposition of scar tissue. The signals to terminate this process fail and progressive scarring of the liver leads to hepatocellular dysfunction and finally death. Up to now fibrosis is untreatable, partly due to complex cell-cell interactions.
Prostaglandins and cytokines regulate all kinds of biological processes in the body. The thesis of Schippers shows that these mediators are not just ‘good’ or ‘bad’ during fibrosis but they act differently in different phases of disease. Her data show that Prostaglandin E2, Interferon γ and alkaline phosphatase in the liver stimulate wound healing in the acute phase of fibrosis, yet they attenuate this disease is in its chronic phase. This dynamic response might be the result of a different cellular composition in both phases. Most importantly, Schippers found that macrophages appear to be able to transform into different cell types with sometimes opposing activities and this transformation appears to be affected by prostaglandin E2 , interferon γ and alkaline phosphatase. This change in scene appears to affect the activities of all players.