Modulation of membrane type 1 matrix metalloproteinase by LPS and gamma interferon bound to extracellular matrix in intestinal crypt cells.

Membrane type 1 matrix metalloproteinase (MT1-MMP) is an integral membrane protein that participates in the processing and degradation of cell surface proteins and the extracellular matrix (ECM). This enzyme regulates ECM turnover in wound repair, promotes cell migration and activates other MMPs, such as MMP-2, which is involved in angiogenesis, cell migration and tumoral metastasis. An increase in pro-inflammatory cytokine expression, such as gamma interferon (IFN-gamma), has been associated with chronic wounds in inflammatory bowel diseases.

Interferon gamma bound to extracellular matrix changes the hyporesponsiveness to LPS in crypt but not villous intestinal epithelial cells.

Intestinal epithelial cells (IEC) are hyporesponsive to LPS. Responsiveness to luminal bacteria has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). In support of this, previous studies have demonstrated that some intestinal epithelial cell lines are induced by IFN-gamma to respond to LPS.