Induction of matrix metalloproteinase-1 by tumor necrosis factor- is mediated by interleukin-6 in cultured fibroblasts of keratoconus
Induction of matrix metalloproteinase-1 by tumor necrosis factor- is mediated by interleukin-6 in cultured fibroblasts of keratoconus
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肿瘤坏死因子对基质金属蛋白酶-1 的诱导是由白介素-6 在培养的圆锥角膜成纤维细胞中介导的
DOI：
10.1177/1535370216650940
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发表时间：
2016-12-01
影响因子：
3.2
通讯作者：
Lan, Weiwei
中科院分区：
文献类型：
--
作者：
Du, Genlai;Liu, Chengxing;Lan, Weiwei
研究发现圆锥角膜患者的泪膜中炎症分子和基质金属蛋白酶（MMP）过度表达。然而，炎症分子和 MMP 在圆锥角膜发病机制中的机制联系仍然难以捉摸。因此，我们研究了肿瘤坏死因子-（TNF-）和白细胞介素-6（IL-6）对MMP-1表达的影响，并使用IL-6抗体（IL-6 Ab）检测IL-6对正常角膜和圆锥角膜成纤维细胞中TNF介导的MMP-1调节的作用。实时聚合酶链反应、酶联免疫吸附试验和Western blot数据表明MMP-1和IL-6在正常角膜和圆锥角膜的成纤维细胞中表达。圆锥角膜中MMP-1和IL-6的水平显着高于正常角膜。 TNF-治疗导致IL-6水平显着增加。 IL-6 治疗诱导正常角膜和圆锥角膜中 MMP-1 的合成。 TNF 以剂量和时间依赖性方式增加 MMP-1 表达，并且这种反应被 IL-6 Ab 完全抑制。总之，这些结果表明圆锥角膜成纤维细胞显示IL-6和MMP-1基因和蛋白质表达水平增加，并且IL-6介导TNF诱导的MMP-1表达。
Inflammatory molecules and matrix metalloproteinase (MMPs) have been found over-expressed in the tear film of patients with keratoconus. However, the mechanistic link between inflammatory molecules and MMPs in the pathogenesis of keratoconus remains still elusive. Therefore, we investigated the effect of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) on MMP-1 expression and used IL-6 antibody (IL-6 Ab) to examine the role of IL-6 on TNF- mediated regulation of MMP-1 in fibroblasts of normal cornea and keratoconus. Real-time polymerase chain reaction, Enzyme-linked immunosorbent assay, and Western blot data demonstrated that MMP-1 and IL-6 were expressed in fibroblasts of normal cornea and keratoconus. Levels of MMP-1 and IL-6 were significantly higher in keratoconus than normal cornea. TNF- treatment led to a significant increase in IL-6 levels. IL-6 treatment induced MMP-1 synthesis in normal cornea and keratoconus. TNF- increased MMP-1 expression in a dose- and time-dependent manner and this response was completely inhibited by the IL-6 Ab. In conclusion, these results indicate that fibroblasts of keratoconus shows increased levels of IL-6 and MMP-1 gene and protein expression and IL-6 mediates the TNF--induced MMP-1 expression.