Cell and Tissue Research

, Volume 351, Issue 2, pp 269–280 | Cite as

Proteases and the gut barrier

  • Paolo Biancheri
  • Antonio Di Sabatino
  • Gino R. Corazza
  • Thomas T. MacDonald
Review

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.

Keywords

Epithelial cell Extracellular matrix Inflammatory bowel disease Mucosal immunology Tumor necrosis factor-alpha 

Abbreviations

ADAM

A disintegrin and a metalloproteinase

IFN

Interferon

Ig

Immunoglobulin

IL

Interleukin

IBD

Inflammatory bowel disease

MMP

Matrix metalloproteinase

MT

Transmembrane domain

TGF

Transforming growth factor

Th

T helper cell type

TIMP

Tissue inhibitor of metalloproteinases

TLR

Toll-like receptor

TNF

Tumor necrosis factor

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Paolo Biancheri
    • 1
    • 2
    • 3
  • Antonio Di Sabatino
    • 1
  • Gino R. Corazza
    • 1
  • Thomas T. MacDonald
    • 2
  1. 1.First Department of Medicine, Fondazione IRCCS Policlinico S. MatteoUniversity of PaviaPaviaItaly
  2. 2.Centre for Immunology and Infectious Disease, Blizard InstituteBarts and the London School of Medicine and DentistryLondonUK
  3. 3.First Department of MedicineFondazione IRCCS Policlinico S. Matteo, University of PaviaPaviaItaly

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