Matrix metalloproteinases in inflammation

• Published in: Biochimica et biophysica acta Vol. 1840; no. 8; pp. 2571 - 2580
• Main Authors: Nissinen, Liisa, Kähäri, Veli-Matti
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2014
• Subjects: Animals; bioactive properties; bioavailability; Cancer; chemokines; growth factors; Humans; immune evasion; Inflammation; Inflammation - enzymology; Inflammation - pathology; Matrix; Matrix Metalloproteinases - chemistry; Matrix Metalloproteinases - metabolism; metalloproteinases; methodology; Models, Biological; neoplasm cells; neoplasms; Neoplasms - enzymology; Neoplasms - pathology; Proteinase; Signaling; substrate specificity; IL; EGF; Proteinase; Inflammation; ADAM-TS; TNF; ADAM; MMP; Signaling; TGF; Matrix; ZO; MCP; Cancer
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2014.03.007

Matrix metalloproteinases (MMPs) are a family of ubiquitously expressed zinc-dependent endopeptidases with broad substrate specificity and strictly regulated tissue specific expression. They are expressed in physiological situations and pathological conditions involving inflammation. MMPs regulate several functions related to inflammation including bioavailability and activity of inflammatory cytokines and chemokines. There is also evidence that MMPs regulate inflammation in tumor microenvironment, which plays an important role in cancer progression. Here, we discuss the current view on the role of MMPs in the regulation of inflammation. MMPs modulate inflammation by regulating bioavailability and activity of cytokines, chemokines, and growth factors, as well as integrity of physical tissue barriers. MMPs are also involved in immune evasion of tumor cells and in regulation of inflammation in tumor microenvironment. There is increasing evidence for non-matrix substrates of MMPs that are related to regulation of inflammatory processes. New methods have been employed for identification of the substrates of MMPs in inflammatory processes in vivo. Detailed information on the substrates of MMPs may offer more specific and effective ways of inhibiting MMP function by blocking the cleavage site in substrate or by inhibition of the bioactivity of the substrate. It is expected, that more precise information on the MMP–substrate interaction may offer novel strategies for therapeutic intervention in inflammatory diseases and cancer without blocking beneficial actions of MMPs. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. •Expression and activity of matrix metalloproteinases is increased in inflammation.•Several inflammatory mediators regulate expression of matrix metalloproteinases.•Matrix metalloproteinases regulate availability and activity of inflammatory mediators.