Metalloproteinases in Inflammatory Bowel Diseases

Abstract

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the gastrointestinal tract, encompassing two main disorders: Crohn's disease (CD) and ulcerative colitis (UC). In both these pathologies, excessive and local immune response against luminal antigens promotes a pathological process leading to various degrees of gut damage. Matrix metalloproteinases (MMPs) are a family of neutral proteases with the ability to degrade all components of extracellular matrix. In physiological conditions, MMPs are produced at very low level and generally in the latent form and are involved in the normal tissue turnover. Their function is inhibited by tissue inhibitors of metalloproteinases (TIMPs). However, in inflamed tissue of IBD patients, MMPs are produced in excess and/or the activity of TIMPs is not sufficient to block MMPs, thereby making a major contribution to the IBD-related mucosal degradation. In this review, we summarize the available evidence on the expression and role of MMPs in IBD.

Keywords: Crohn’s disease; intestinal inflammation; tissue inhibitor of metalloproteinases; ulcerative colitis.

Figure 1

Schematic view illustrating how a specific matrix metalloproteinase (MMP) (eg, MMP-3 [A]) triggers the conversion of other MMP zymogens (proMMP-7 [B], proMMP-9 [C], or proMMP-13 [D]) to their active forms.

Figure 2

Schematic view of situations in which MMP is either controlled or not by tissue inhibitors of MMPs (TIMPs). (A) In physiological conditions, TIMPs form with MMPs reversible complexes in a 1:1 ratio thereby controlling MMP activity. Within inflammatory microenvironment, the TIMP/MMP ratio can be decreased by overexpression of MMPs without a parallel increase of TIMPs (B), a sudden decrease in the expression of TIMPs (C) or increased MMP concentration that is accompanied by concomitant decrease in TIMP levels (D).