title: Proteases and the gut barrier.
abstract: Serine proteases, cysteine proteases, aspartic proteases and matrix metalloproteinases play an essential role in extracellular matrix remodeling and turnover through their proteolytic action on collagens, proteoglycans, fibronectin, elastin and laminin. Proteases can also act on chemokines, receptors and anti-microbial peptides, often potentiating their activity. The intestinal mucosa is the largest interface between the external environment and the tissues of the human body and is constantly exposed to proteolytic enzymes from many sources, including bacteria in the intestinal lumen, fibroblasts and immune cells in the lamina propria and enterocytes. Controlled proteolytic activity is crucial for the maintenance of gut immune homeostasis, for normal tissue turnover and for the integrity of the gut barrier. However, in intestinal immune-mediated disorders, pro-inflammatory cytokines induce the up-regulation of proteases, which become the end-stage effectors of mucosal damage by destroying the epithelium and basement membrane integrity and degrading the extracellular matrix of the lamina propria to produce ulcers. Protease-mediated barrier disruption in turn results in increased amounts of antigen crossing into the lamina propria, driving further immune responses and sustaining the inflammatory process.
authors.affiliation: First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Piazzale Golgi 5, 27100, Pavia, Italy. paolo.biancheri@gmail.com
authors.forename: Paolo
authors.initials: P
authors.lastname: Biancheri
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Sabatino
authors.forename: Gino R
authors.initials: GR
authors.lastname: Corazza
authors.forename: Thomas T
authors.initials: TT
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000201:enzymology; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology*; D007422:Intestines / Q000201:enzymology; D010447:Peptide Hydrolases / Q000378:metabolism*
chemical_list: D010447:Peptide Hydrolases