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

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
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DOI:
10.1016/s0006-2952(98)00257-3
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发表时间:
1998-12-01
影响因子:
5.8
通讯作者:
Pellat, B
Pellat, B
中科院分区:
医学2区
文献类型:
--
作者:
Gogly, B;Hornebeck, W;Pellat, B

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在此,我们描述了肝素对人牙龈成纤维细胞 (HGF) 中白介素 1-β (IL-1 β) 诱导的胶原酶(基质金属蛋白酶-1,MMP-1)、基质溶素-1(基质金属蛋白酶-3,MMP-3)和基质金属蛋白酶组织抑制剂 - 1 (TIMP-1) 表达的影响。在 HGF 培养基中添加 2 ng/mL IL-1 beta 后,分泌酶和抑制剂的量及其 mRNA 稳态水平显着增加。 IL-1β后1小时向细胞培养基中添加肝素会以剂量依赖性方式降低MMP和TIMP-1的表达。肝素在低至1μg/mL浓度时抑制作用显着。这些发现可以用缺乏抗凝活性的低 M-r 肝素片段来重现。因此,肝素和碎片可能会降低炎症期间牙龈成纤维细胞的过度蛋白水解能力,并且可以用作牙龈炎和牙周炎的药物。生物化学制药 56;11:1447-1454, 1998。(C) 1998 Elsevier Science Inc.
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.