Subproject 5

Which impact does the proteosomal induced immune response have during pancreatitis?

 

Pancreatitis is a primary sterile disease, there are no bacterial or viral pathogens inducing an immune reaction. Despite the absence of pathogens, 10 - 20 % of patients develop a severe systemic inflammation associated with complications like organ failure. This severe form of pancreatitis is also associated with a high mortality ratio (10 - 20 %). The exact mechanism behind this severe immune response is not well understood so far.

Pancreatic acinar cells produce and secrete large amounts of digestive enzymes: They have the highest protein synthesis activity in the human body. To prevent protein overproduction that can lead to ER-stress by accumulation of excess proteins, protein waste is removed by proteasomal degradation pathways. The proteasome degrades proteins and making the amino acids available again to the metabolism of the cell. In some cases the proteasome complex has the ability to induce an immune response, these forms were called immunoproteasome. The aim of this subproject is to investigate the role of proteasome mediated immune response in the progression of pancreatitis. One research question focuses on whether acinar cells mediate the immune response by inducing immunoproteasome. Beside acinar cells also macrophages and other cells of the immune system, which transmigrate in a high amount to the pancreas, express the immunoproteasome complex. This is maybe a mechanism which drives the immune reaction and leads to a so called systemic inflammatory response syndrome (SIRS). The effect of the immunoproteasome in the progression of pancreatitis is to be studied in a mouse model of pancreatitis in wild type as well as immunoproteasome knockout mice. The immune regulatory mechanism behind the disease should be explored with a closer look on therapeutic options for patients' treatment.

 

 

Supervisors

Prof. Dr. med. Markus M. Lerch

Prof. Dr. rer. nat. Elke Krüger

Dr. rer. nat. Matthias Sendler

 

Team

Dr. rer. nat. Laura De Freitas Chama

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