The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells

Abstract

SUMMARYIt has been suggested that lL-1 produces cartilage matrix degradation by metalloproteinasessuch as collagenase, and that such degradation is regulated by metalloproteinase inhibitors (TIMP). Therefore, the balanee between collagenase and TIM Pis an important factor for tissue destruction in inflammatory joints. In the present study the efiects of cytokines on collagenase and TIMP production in chondroeytes as welt as the effects of cytokines on TIMP production in connective tissue cells were studied. IL-I^ inhibited TIMP production in endothelial cells while enhancing TIMP production in synovial cells and chondrocytes. In addition, tumour necrosis factor-alpha (TNF-x) significantly inhibited and IL-6 significantly enhanced TIMP production in endothelial cells, synovial eells and chondroeytes. In tbe chondrocytc supernatant, collagenase activity/TIMP ratio was significantly elevated by the addition of either IL-!^ or TNF-a: to the cells, whereas the ratio was significantly decreased by IL-6. These results suggest that the cytokine eflects on TIMP production are different among the dilTerent cell types, and that either IL-l/f or TNF-a induce cartilage matrix degradation by disrupting the collagenase/TIMP balance, while, on the other hand, lL-6 protects the tissue through an opposite effect.

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