Inflammatory Response in Patients With Ulcerative Colitis
Inflammatory Response in Patients With Ulcerative Colitis
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that affects intestinal mucosa. The pathogenic mechanisms of UC are complex and involve interaction between genetic, host immune system and environmental factors. One of the major factors in the onset of UC is inappropriate mucosal immune response towards the intestinal microbiota leading to mucosal tissue damage and chronic inflammation.
Increased production of reactive oxygen species (ROS) and oxidant-induced protein or lipid alterations have been implicated in tissue damage observed in chronic inflammatory disorders, such as IBD. The key producers of the superoxide anions in the colon are non-phagocytic and phagocytic cells. The epithelial NADPH oxidase homologs (Nox1, Nox3, Nox4, Nox5, DUOX1, and DUOX2) generate a higher level of superoxide in the colon compared to phagocyte NADPH oxidase. Previous studies have shown that epithelial NADPH oxidase mediating formation of ROS might be involved in host defence system and inflammatory responses at mucosal surfaces. ROS production in the intestinal mucosal biopsies is increased during inflammation. Moreover, genetic mutations in genes encoding components of the NADPH complex have been associated with IBD susceptibility. The variations have been found in genes responsible for localization of the NADPH oxidase complex (including p47phox and p67phox and RAC2) to the membrane.
Despite the profound consequences of either absent or excessive ROS generation in the intestinal tract, little is known about the molecular pathways controlling ROS production via NOX enzymes in the primary intestinal epithelial cells derived from UC patients. Therefore, in this study we aimed to evaluate the role of NADPH oxidase in primary intestinal epithelial cells during the active phase of UC.
Background
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that affects intestinal mucosa. The pathogenic mechanisms of UC are complex and involve interaction between genetic, host immune system and environmental factors. One of the major factors in the onset of UC is inappropriate mucosal immune response towards the intestinal microbiota leading to mucosal tissue damage and chronic inflammation.
Increased production of reactive oxygen species (ROS) and oxidant-induced protein or lipid alterations have been implicated in tissue damage observed in chronic inflammatory disorders, such as IBD. The key producers of the superoxide anions in the colon are non-phagocytic and phagocytic cells. The epithelial NADPH oxidase homologs (Nox1, Nox3, Nox4, Nox5, DUOX1, and DUOX2) generate a higher level of superoxide in the colon compared to phagocyte NADPH oxidase. Previous studies have shown that epithelial NADPH oxidase mediating formation of ROS might be involved in host defence system and inflammatory responses at mucosal surfaces. ROS production in the intestinal mucosal biopsies is increased during inflammation. Moreover, genetic mutations in genes encoding components of the NADPH complex have been associated with IBD susceptibility. The variations have been found in genes responsible for localization of the NADPH oxidase complex (including p47phox and p67phox and RAC2) to the membrane.
Despite the profound consequences of either absent or excessive ROS generation in the intestinal tract, little is known about the molecular pathways controlling ROS production via NOX enzymes in the primary intestinal epithelial cells derived from UC patients. Therefore, in this study we aimed to evaluate the role of NADPH oxidase in primary intestinal epithelial cells during the active phase of UC.
