TNF-α Stimulates MMP-2 and MMP-9 Activities in Human Corneal Epithelial Cells via the Activation of FAK/ERK Signaling

被引:48
作者
Yang, Yan-Ning [1 ]
Wang, Fang [1 ]
Zhou, Wei [2 ]
Wu, Zhi-Qing [1 ]
Xing, Yi-Qiao [1 ]
机构
[1] Wuhan Univ, Renmin Hosp, Dept Ophthalmol, Wuhan 430060, Peoples R China
[2] Wuhan Univ, Renmin Hosp, Inst Gastroenterol & Hepatol, Wuhan 430060, Peoples R China
关键词
Herpes simplex keratitis; Herpes simplex virus type 1; Tumor necrosis factor-alpha; Focal adhesion kinase; Extracellular regulated protein kinase; HERPETIC STROMAL KERATITIS; NECROSIS-FACTOR-ALPHA; MATRIX METALLOPROTEINASES; INFLAMMATORY CYTOKINES; TISSUE INHIBITORS; SIMPLEX-VIRUS; FAK; PATHOGENESIS; MODEL;
D O I
10.1159/000338819
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Aims: Herpes simplex virus type-1-induced herpes simplex keratitis (HSK) is a common immunological cornea disease. While previous studies have addressed the role of tumor necrosis factor (TNF)-alpha and matrix metalloproteinases (MMPs) in HSK, the mechanistic link between TNF-alpha and MMPs in the pathogenesis of HSK remains elusive. Methods: We first established a HSK mice model and measured the levels of TNF alpha, MMP-2 and MMP-9 in the corneas at different time points by ELISA. Next, we employed cultured human corneal epithelial (HCE) cells as an in vitro model and performed gelatin zymography analysis. Results: We observed that the change in the TNF-alpha level shared a similar pattern to that of MMP-2 and MMP-9 in the HSK mice model. Furthermore, TNF-alpha stimulated MMP-2 and MMP-9 activities in a dose-dependent manner, but either knockdown of focal adhesion kinase (FAK) by short interference RNA or inhibition of extracellular regulated protein kinase (ERK) by chemical inhibitor could block TNF-alpha-stimulated MMP-2 and MMP-9 activities in vitro. Taken together, our results provide in vivo evidence that the TNF-alpha level is positively correlated with MMP-2 and MMP-9 levels in a HSK model and in vitro evidence that TNF-alpha stimulates MMP-2 and MMP-9 activities via the activation of FAK/ERK signaling in HCE cells. Conclusions: Our findings shed new light on the pathogenesis of HSK and open up new possibility of modulating the TNF-alpha- FAK-ERK signaling cascade to pursue therapeutic measures for HSK. Copyright (c) 2012 S. Karger AG, Basel
引用
收藏
页码:165 / 170
页数:6
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