The dual personalities of matrix metalloproteinases in inflammation.
Collagen, gelatin, elastin, fibronectin, proteoglycans and vitronectin are just a few proteins which form the "mesh" that holds a multicellular organism together. The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade the extracellular matrix. Over several decades it has been clearly established that MMPs are the key molecules associated with matrix remodeling. The remodeling of this matrix is important for physiological and pathological processes such as pregnancy, wound repair, cancer and arthritis. The identification of new non-matrix MMP substrates involved in inflammation, highlights the diverse role of MMPs. These enzymes can enhance leukocyte invasion and regulate the inflammatory activity of serine proteases, cytokines and chemokines. Interestingly, the MMP family appears to have a "dual personality" in that several MMPs such as MMP-2 and -9 can favour either anti- or pro-inflammatory action, respectively. The extent of this dual functionality of MMPs is yet to be realized. Elucidating these processes may assist in the development of drugs for the treatment of inflammatory diseases such as arthritis, cancer and chronic wounds.
Le
Nghia T V
NT
Sutton Arthritis Research Laboratories, Institute for Bone and Joint Research, University of Sydney, Level 1, Building 35, Royal North Shore Hospital, St Leonards, New South Wales, 2065, Australia.
Xue
Meilang
M
Castelnoble
Laura A
LA
Jackson
Christopher J
CJ
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D018836:Inflammation Mediators / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000201:enzymology; D012697:Serine Endopeptidases / Q000378:metabolism; D014945:Wound Healing
D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D012697:Serine Endopeptidases; D020782:Matrix Metalloproteinases