Mohammed F F, Smookler D S, Khokha R
Ontario Cancer Institute/University Health Network, Toronto, Canada.
Ann Rheum Dis. 2003 Nov;62 Suppl 2(Suppl 2):ii43-7. doi: 10.1136/ard.62.suppl_2.ii43.
Ideally, the inflammatory response occurs rapidly to terminate infection. It also must halt in a timely manner to stop this reaction from inflicting self damage. Such a highly regulated process results from altering balances in pro- and anti-inflammatory signals orchestrated by multiple cell types and factors within the tissue microenvironment. The discovery of new substrates of metalloproteinases within this microenvironment has disclosed a new function in inflammation. The role of these proteases now extends beyond extracellular matrix remodelling enzymes to that of mediators of inflammatory signals involving various chemokines and cytokines. As natural inhibitors of these metalloproteinases, TIMPs have the potential of regulating the inflammatory response and affecting diseases such as rheumatoid arthritis. TIMP-3, in particular, stands out as an important regulator of inflammation with its ability to specifically inhibit proinflammatory cytokines and tissue destruction in the joint.
理想情况下，炎症反应会迅速发生以终止感染。它还必须及时停止，以防止这种反应造成自身损伤。这样一个高度调控的过程是由组织微环境中多种细胞类型和因子精心编排的促炎和抗炎信号平衡的改变所导致的。在这个微环境中金属蛋白酶新底物的发现揭示了炎症中的一种新功能。这些蛋白酶的作用现在已经从细胞外基质重塑酶扩展到涉及各种趋化因子和细胞因子的炎症信号介质。作为这些金属蛋白酶的天然抑制剂，组织金属蛋白酶抑制剂（TIMPs）具有调节炎症反应和影响类风湿性关节炎等疾病的潜力。特别是TIMP-3，因其能够特异性抑制促炎细胞因子和关节中的组织破坏，而成为炎症的重要调节因子。
