P4 - AG Westendorf Jana Ebel

Role of acid sphingomyelinase/ceramidase in gut infection and inflammation

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, which is characterized by repeated cycles of mucosal damage, ulceration and regeneration. The inflammatory disorder is influenced by genetic and environmental factors such as diet, microbiota composition and infections. The impairment of the epithelial barrier function was shown to play an important role in IBD pathogenesis and is further associated with a dysregulation of several sphingolipid molecules. Inflammatory cytokines involved in the colon pathology cause alterations of the lipid composition in the cell membrane by activation of various phospholipases, sphingomyelinases and other lipid modifying enzymes. However, little is known about the role of the sphingolipid system, including acid sphingomyelinase (Asm) and acid ceramidase (Ac) on the intestinal barrier in the context of gut infection. In the present project, we analyze and compare the contribution of Asm and Ac on the intestinal epithelial barrier function in pathogen-induced enterocolitis. Detailed knowledge on the impact of the acid sphingomyelinase/ceramidase system in intestinal homeostasis and inflammation will allow the development of new and more specific therapeutic strategies for IBD.