Proteases and small intestinal barrier function in health and disease.
OBJECTIVE
To summarize the recent knowledge regarding intestinal proteases and the gut barrier.


RESULTS
It is now well established that intestinal proteases, such as matrix metalloproteinase (MMP)-1, MMP-3, MMP-10 and MMP-12, are key players in the development of ulcers in inflammatory bowel disease, have direct effects on epithelial barrier function and are involved in epithelial restitution. However, more recent work has suggested that the membrane-anchored epithelial cell serine protease matriptase is critical in maintaining the gut barrier, and roles have also been described for elastase, MMP-13, gelatinases, mast cell proteases and proteases derived from parasites and gut bacteria. Interestingly, epithelial proteases often co-localize with epithelial adherens junctions, and nonepithelial-derived proteases have junctional proteins as targets.


CONCLUSIONS
The role of proteases in controlling normal barrier function in the gut is now becoming very clear, to go alongside their role in intestinal inflammation.
Centre for Immunology and Infectious Disease, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK *Paolo Giuffrida and Paolo Biancheri contributed equally to the writing of this article and should be considered joint first authors.
Paolo
P
Giuffrida
Paolo
P
Biancheri
Thomas T
TT
MacDonald
D004847:Epithelial Cells / Q000201:enzymology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000201:enzymology* / Q000503:physiopathology; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000201:enzymology; D007421:Intestine, Small / Q000201:enzymology / Q000502:physiology*; D008407:Mast Cells / Q000201:enzymology; D010447:Peptide Hydrolases / Q000502:physiology*
D010447:Peptide Hydrolases