The Receptor for Advanced Glycation Endpoducts (RAGE) in mucosal damage and immunity

The Receptor for Advanced Glycation Endpoducts (RAGE) is a 35kDa multiligand receptor of the immunoglobulin superfamily that is able to recognize a wide range of endogenous molecules released upon inflammation and injury superfamily. Beneath its ability to recognise molecules modified by advanced glycation end products (AGEs), which occur through an irreversible reaction of proteins and lipids with glucose, RAGE has been described to interact with a variety of molecules. Endogenous molecules such as high mobility group protein box 1 (HMGB1), members of the S100 protein family (S100A9 and S100A12), Amyloid beta and others have been identified as ligands of RAGE.

It has become clear that the host response to inflammation is not limited to the interaction of immune cells with pathogens but is also mediated by endogenous proteins collectively termed “danger associated molecular patterns” (DAMPs) or alarmins binding to receptors such as RAGE. Interaction of these molecules with RAGE activates pro-inflammatory signaling cascades, involving Nuclear Faktor κB (NF‑κB), Mitogen Activated Protein Kinase (MAP‑Kinase) and other pro-inflammatory mediators. Soluble RAGE (sRAGE) that lacks the transmembrane and signaling domain can compete with full length RAGE thereby reducing pro-inflammatory reactions.

RAGE is expressed on monocytes and macrophages and is associated with many (auto)inflammatory disorders like rheumatoid arthritis, diabetes, neurodegenerative disorders, arteriosclerosis and others. Ulcerative colitis and Chrohn’s disease are inflammatory disorders of epithelial colon tissue. It is suspected that these diseases are linked to the expression of inflammatory mediators and the induction of oxidative stress by immune cells. A first hint for the involvement of RAGE in these disorders comes from a subgroup of Chron’s disease patients who expressed elevated levels of sRAGE and were found to be partially protected from the disease, due to polymorphisms in the RAGE gene (Däbritz et al., 2011).

However, the exact mechanism by which RAGE influences the development of inflammatory processes in the gastrointestinal tract is not yet determined. Furthermore, as dysfunctional Monocytes and Macrophages seem to be a major factor in the development of intestinal inflammation, it is not clear whether RAGE influences the function of these cells in the intestine. Hence, we are particularly interested in the role of RAGE in mucosal damage and immunity in the gut.


Project Responsibles:

Toni Weinhage, PhD

Melanie Saers, MTA