Matrix metalloproteinases as drug targets in infections caused by gram-negative bacteria and in septic shock.
The mammalian immune system is optimized to cope effectively with the constant threat of pathogens. However, when the immune system overreacts, sepsis, severe sepsis, or septic shock can develop. Despite extensive research, these conditions remain the leading cause of death in intensive care units. The matrix metalloproteinases (MMPs) constitute a family of proteases that are expressed in developmental, physiological, and pathological processes and also in response to infections. Studies using MMP inhibitors and MMP knockout mice indicate that MMPs play essential roles in infection and in the host defense against infection. This review provides a brief introduction to some basic concepts of infections caused by gram-negative bacteria and reviews reports describing MMP expression and inhibition, as well as studies with MMP-deficient mice in models of infection caused by gram-negative bacteria and of septic shock. We discuss whether MMPs should be considered novel drug targets in infection and septic shock.
Vanlaere
Ineke
I
Department for Molecular Biomedical Research, VIB, B-9052 Ghent, Belgium.
Libert
Claude
C
D000818:Animals; D006090:Gram-Negative Bacteria; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D012772:Shock, Septic / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control
D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases