MMPs, ADAMs and their natural inhibitors in inflammatory bowel disease: involvement of oxidative stress

Matrix metalloproteinases (MMPs) are enzymes involved in the degradation of extracellular matrix proteins and in several functions such as wound repair. The regulation of MMPs occurs at various levels including expression and inhibition by tissue specific inhibitors of MMPs (TIMPs). An alteration of intracellular redox state can modulate the activation and/or expression of MMPs. The increased expression and activity of MMPs are related to inflammatory state and pathogenesis of inflammatory bowel disease (IBD). In particular, an imbalance between MMPs and TIMPs is present at intestinal level in IBD, and this can be responsible of alterations of different processes such as repair of damaged mucosa, function and migration of immune cells and mucosal ulceration. A disintegrin and metalloproteinase 17 (ADAM17), belonging to ADAM family, plays an important role in the intestinal inflammation and increases in human colonic mucosa of IBD patients. In this review we report the effects of MMP, ADAM17 and TIMP altered levels on damage amplification the caused by inflammation and oxidative stress in IBD. Moreover, the review evidences the role of the intracellular redox state and antioxidants on regulation of expression and activity of some MMPs in condition of oxidative stress in IBD.