Signal pathways involved in the production of MMP-1 and MMP-3 in human gingival fibroblasts
Signal pathways involved in the production of MMP-1 and MMP-3 in human gingival fibroblasts
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DOI：
10.1034/j.1600-0722.2002.21247.x
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发表时间：
2002-08-01
影响因子：
1.9
通讯作者：
Modéer, T
中科院分区：
文献类型：
--
作者：
Domeij, H;Yucel-Lindberg, T;Modéer, T
牙周炎与细胞因子、前列腺素和基质金属蛋白酶（MMPs）的产生增加有关。本研究的目的是研究在白细胞介素-1 β (il -1 β)、肿瘤坏死因子α (TNFalpha)或表皮生长因子（EGF）激发的人牙龈成纤维细胞中MMP-1和MMP-3的产生和调控。结果表明，牙龈成纤维细胞组成性地产生MMP-1和MMP-3，细胞因子il -1 β、TNFalpha和EGF增加了牙龈成纤维细胞中MMP-1和MMP-3的产生。细胞因子的上调在培养8 h时表现明显，随后在培养48 h时持续升高。il -1 β或TNFalpha诱导的MMPs上调被环氧合酶-2 （COX-2）抑制剂NS-398、p38 map -激酶抑制剂SB 203580和酪氨酸激酶抑制剂herbimycin a降低。此外，il -1 β、TNFalpha或EGF诱导的MMP-1和MMP-3的产生在糖皮质激素地塞米松的存在下被强烈降低。我们的研究结果表明，细胞因子il -1 β、TNFalpha和EGF分别促进人牙龈成纤维细胞中MMP-1和MMP-3的产生，并且信号通路COX-2、map -激酶和酪氨酸激酶部分参与了mmp的产生。
Periodontitis is associated with enhanced production of cytokines, prostaglandins and matrix metalloproteinases (MMPs). The aim of this study was to investigate the production and regulation of MMP-1 and MMP-3 in human gingival fibroblasts challenged with the cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) or epidermal growth factor (EGF). The results showed that gingival fibroblasts constitutively produce MMP-1 and MMP-3, and that the cytokines IL-1beta, TNFalpha and EGF increase both MMP-1 and MMP-3 production in gingival fibroblasts. The upregulation by the cytokines was apparent at 8 h of incubation and increased thereafter continuously during 48 h of incubation. The upregulation of MMPs, induced by IL-1beta or TNFalpha, was reduced by the cyxlooxygenase-2 (COX-2) inhibitor NS-398, the p38 MAP-kinase inhibitor SB 203580, and the tyrosine kinase inhibitor herbimycin A. In addition, MMP-1 and MMP-3 production, induced by IL-1beta, TNFalpha or EGF, was strongly reduced by the presence of the glucocorticoid dexamethasone. Our findings demonstrate that the cytokines IL-1beta, TNFalpha and EGF, respectively, enhance both MMP-1 and MMP-3 production in human gingival fibroblasts, and that the signal pathways COX-2, MAP-kinases and tyrosine kinases are partly involved in the production of MMPs.