Proteases/Antiproteases in Inflammatory Bowel Diseases

Abstract

Protein turnover is orchestrated by a large array of proteases, and the gastrointestinal tract is the organ the most exposed to proteases, whether they originate from the pancreas for digestive purpose, from resident cells, from infiltrated inflammatory cells, or from microorganisms present in the intestinal lumen. To maintain tissue homeostasis, the gastrointestinal tract has developed mechanisms that tightly regulate the proteolytic balance in the tissues. Those mechanisms range from physical barriers (mucus layer, tight control of intestinal epithelial cell para-and transcellular passages) to molecular control of proteolytic activity through endogenous protease inhibitors. In the setting of inflammation, gastrointestinal tissues are overflowed with massive proteolytic activity that contributes to the generation of inflammatory symptoms. The present chapter analyses the disruption of the protease-antiprotease balance in the context of inflammatory bowel disease. It proposes to review the type of proteases that are present in the gastrointestinal tract, their known effects on the generation and/or maintenance of inflammatory symptoms, and their mechanisms of action. Further, the role of endogenous protease inhibitors is discussed, as well as the potential use of protease inhibition, as new possible therapeutic approach to treat chronic inflammatory disorders of the gut.