The Good and the Bad Side of Heme-Oxygenase-1 in the Gut

Mucosal immunity in the gut has the important task of protecting an organism against potential danger, but at the same time of staying silent in response to harmless antigens present in the intestinal lumen. The delicate balance between immune activation and tolerance is referred to as gut homeostasis. It has become clear that different types of immune cells and several factors participate in the maintenance of gut homeostasis, having as a final goal the prevention of non-necessary inflammation. Immune cells of the myeloid lineage, such as macrophages located in the lamina propria, represent the most abundant leukocyte population in the intestine and play a critical role in keeping the immune system silent, via the production of the anti-inflammatory cytokine interleukin-10. Gut macrophages are an important source of the oxidative enzyme heme-oxygenase-1 (HO-1), which has crucial immune-modulatory properties. The protective role of HO-1 in the control of the intestinal inflammation, and its connection with the enteric flora have been demonstrated in experimental settings as well as in human biological samples. Loss of the gut homeostasis gives rise to conditions of acute inflammation that may degenerate into chronic disease, eventually leading to carcinogenesis. Understanding the mechanisms that regulate this enzyme will disclose novel therapeutic approaches that are designed to control chronic inflammation in the intestine.