Chronic inflammatory diseases

Inflammation is a natural process to prevent infection. However, malfunctioning of the immune system can lead to chronic inflammation, allergies and disease

Studies of NOD2/ p22phox interaction: studying the interplay between innate immune receptors and ROS-producing enzymes in inflammatory disease

Research project at the Institute of Clinical Molecular Biology (icmb), cell biology group (supervision by Dr. Simone Lipinski, Prof. Dr. Philip Rosenstiel)

Reactive oxygen species (ROS) can be produced as a byproduct in biological reactions or as a primary function of the NADPH oxidase (NOX) complex. ROS-generating enzymes are evolutionary highly conserved and have been identified in a wide variety of organisms, including mammals, nematodes and plants (Kawahara et al., 2007). ROS play pivotal roles in cell signaling, host defence, and inflammation. Due to their high biochemical reactivity, ROS can protect against pathogens but they can also cause tissue damage by unspecific oxidation (oxidative stress).

Epithelial cells and mucosal surfaces form a direct interface between organism and invaders. We think that a crosstalk between ROS-producing enzymes and receptors of the innate immune system is critical to maintain the integrity and function of this part of the immune system. It has already been shown that inflammatory disorders such as the inflammatory bowel disease CD (Crohn’s disease) are connected with oxidative stress in affected tissues.

Here, we hypothesized that the innate immune receptor NOD2, which has been shown to play a role in the etiology of Crohn’s disease, interacts with the the NADPH oxidase component p22phox. We showed that NOD2 and p22phox co-localize upon activation and that there is a direct protein-protein interaction potentially involved in production of reactive oxygen species.

NOD2 and p22phox co-localize in co-transfected HEK-293 cells. NOD2 was stained with a green fluorescent dye (FITC), p22phox was stained with a red fluorescent dye (Cy3); the nuclei were stained with the DNA intercalating dye DAPI (blue signal). A yellow color in this overlay indicates overlapping signals from red and green and, hence, co-localization of the two proteins.

The corresponding publication can be found here