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Nat Rev Immunol. 2013 Sep;13(9):649-65. doi: 10.1038/nri3499.

Metalloproteinases and their natural inhibitors in inflammation and immunity.

Author information

1
Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario M5P 1H6, Canada. rkhokha@uhnres.utoronto.ca

Abstract

Over the past 50 years, steady growth in the field of metalloproteinase biology has shown that the degradation of extracellular matrix components represents only a fraction of the functions performed by these enzymes and has highlighted their fundamental roles in immunity. Metalloproteinases regulate aspects of immune cell development, effector function, migration and ligand-receptor interactions. They carry out ectodomain shedding of cytokines and their cognate receptors. Together with their endogenous inhibitors TIMPs (tissue inhibitor of metalloproteinases), these enzymes regulate signalling downstream of the tumour necrosis factor receptor and the interleukin-6 receptor, as well as that downstream of the epidermal growth factor receptor and Notch, which are all pertinent for inflammatory responses. This Review discusses the metalloproteinase family as a crucial component in immune cell development and function.

PMID:
23969736
DOI:
10.1038/nri3499
[Indexed for MEDLINE]
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