Matrix metalloproteases role in bowel inflammation and inflammatory bowel disease: an up to date review.

There has been an explosion of literature in recent years highlighting the pivotal role of matrix metalloproteases (MMPs) in the immune response. This review will focus on our current understanding of MMPs in the gastrointestinal tract and in particular the field of inflammatory bowel disease. MMPs are structurally similar proteins that classically degrade extracellular components. In the gastrointestinal tract, they are involved in the physical maintenance and turnover of the intestinal barrier, aid in leukocyte recruitment, regulate the activity of cytokines, chemokines, and growth factors. During inflammation, numerous MMPs are upregulated in the bowel and play a key role in the resolution of inflammation and wound healing during the normal immune response. In humans, an aberrant expression has been extensively documented in inflammatory bowel disease implicating them in tissue degradation, persistence of the inflammatory state and fibrosis. Animal studies in particular knockout mouse models have provided insight into the importance of individual MMPs in bowel homeostasis and inflammation. Endogenous inhibitors of MMPs such as tissue inhibitors of MMPs (TIMPs) and alpha-2 macroglobulin maintain the balance between extracellular matrix deposition and degradation. An imbalance between MMPs and their inhibitors through genetic variation, gene expression abnormalities, or environmental effects can directly impact on tissue homeostasis resulting in tissue damage and prolonged inflammation. In the future, targeting MMPs or their inhibitors could be a possible therapeutic option. The challenge will be achieving selectivity.