Influence of heparin(s) on the interleukin-1-β-induced expression of collagenase, stromelysin-1, and tissue inhibitor of metalloproteinase-1 in human gingival fibroblasts

Here, we describe the influence of heparin(s) on the interleukin-1-beta (IL-1 beta)-induced expression of collagenase (matrix metalloproteinase-1, MMP-1), stromelysin-1 (matrix metalloproteinase-3, MMP-3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in human gingival fibroblasts (HGF). Amounts of secreted enzymes and inhibitors as well as their mRNA steady-state levels increased significantly following supplementation of HGF culture medium with 2 ng/mL of IL-1 beta. Addition of heparin to cell culture medium 1 hour following IL-1 beta decreased MMP and TIMP-1 expression in a dose-dependent manner. The inhibitory effect of heparin was significant at a concentration as low as 1 mu g/mL. These findings could be reproduced with a low M-r heparin fragment devoid of anticoagulant activity. Heparin and fragments might therefore reduce the excessive proteolytic capacity of the gingival fibroblast during inflammation and could be useful as pharmacological agent(s) in gingivitis and periodontitis. BIOCHEM PHARMACOL 56;11:1447-1454, 1998. (C) 1998 Elsevier Science Inc.