A German research team has identified a mechanism that can prevent ulcerative colitis, or inflammation of the colon. It is known that the bacteria in the intestinal flora and malfunctions of the immune system are responsible for theDevelopment of chronic intestinal diseasesare responsible. This causes epithelial cells in the intestinal wall to die, which could even cause colon cancer. The study authors have now managed to prevent this cell death in recent experiments with mouse models. The study results could provide a promising future therapeutic approach.
In patients with chronic inflammatory bowel disease, more cells in the intestinal wall die. Bacteria then move from the inside of the intestine into the damaged intestinal wall, causing inflammation and further cell death. The epithelial barrier, the barrier between the intestinal contents and the intestinal wall, also becomes more permeable. As cell death increases, the disease also progresses as more and more bacteria settle in the damaged intestinal wall. The authors of this research describe this as a vicious circle. Now Prof. Dr. Christoph Becker and his colleagues from the University Hospital in Erlangen have found a mechanism that could prevent cell death and thus break the vicious circle. In mice and tissue from patients, researchers found that a messenger called prostaglandin E2 can protect epithelial cells from a special form of cell death (necroptosis). Prostaglandins are hormone-like messenger substances that have various effects in the organism. However, it is not yet entirely clear how prostaglandins regulate inflammatory processes.
Prostaglandin E2 prevents necroptosis by binding to EP4 receptors on epithelial cells. The more of these receptors are activated, the fewer cells die, according to the study authors. Patients with high EP4 levels on the cell surface show a milder course of the disease than patients with low EP4 levels. The activation of the receptors by prostaglandin E2 counteracts the progression of colon inflammation. Together with colleagues in Canada, the research team tested an artificially produced molecule that can activate the EP4 receptor like prostaglandin E2. Treatment with this molecule could prevent excessive cell death in the intestinal barrier and block bacterial invasion. The findingsthis studyoffer a promising new therapeutic approach against ulcerative colitis and other chronic inflammatory bowel diseases.
