DEGRADATION OF INTERLEUKIN-1-BETA BY MATRIX METALLOPROTEINASES

Matrix metalloproteinases (MMPs) and interleukin 1 (IL-1) are implicat ed in inflammation and tissue destruction, where IL-1 is a potent stim ulator of connective tissue cells to produce the extracellular matrix- degrading MMPs. Here, we report that IL-1 beta, but not IL-1 alpha, is degraded by MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), M MP-3 (stromelysin 1), and MMP-9 (gelatinase B). This degradation was e ffectively blocked by tissue inhibitor of metalloproteinases (TIMP)-1. When IL-1 beta was treated with MMPs it lost the ability to enhance t he synthesis of prostaglandin E(2) and pro-MMP-3 in human fibroblasts. The primary cleavage site of IL-1 beta by MMP-2 was identified at the Glu(25)-Leu(26) bond. These results suggest that IL-1 beta stimulates connective tissue cells to produce MMPs, but activated MMPs in turn n egatively regulate the activity of IL-1 beta.