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首页> 外文期刊>Journal of Cellular Physiology >MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions
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MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions

机译:MMP-8对地塞米松治疗至关重要干眼条件下Alkali-Burned眼角膜

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摘要

Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix-metalloproteinases (MMPs -1,-3,-9,-13), IL-1 beta and IL-6, while it significantly increased MMP-8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP-8 induction is responsible for some of the protective effects of Dex in CM, MMP-8 knock out mice (MMP-8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 mu l of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP-8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP-8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL-6, CXCL1, and MMP-1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP-8KO mice. These results suggest that some of the anti-inflammatory effects of Dex are mediated through increased MMP-8 expression. (C) 2016 Wiley Periodicals, Inc.
机译:我们先前的研究已经表明,地塞米松(敏捷)的表达减少基质金属蛋白酶(MMPs 1、3、9,-13),βil - 1和il - 6,而显著增加MMP-8 mRNA转录相伴干眼病和角膜碱烧伤小鼠模型(厘米)。负责的部分保护作用敏捷在厘米,MMP-8敲除小鼠(MMP-8KO)受到CM 2或5天,局部要么2μl为0.1%地塞米松治疗(敏捷),或生理盐水QID。老鼠敏捷或BSS和局部治疗收到100 nM CAM12 (MMP-8抑制剂)或汽车的IP, QD。敏捷MMP-8KO治疗小鼠受到CM显示减少角膜透明度,增加表达的炎症介质(il - 6,处于受控和金属蛋白酶- 1信使rna)和增加中性粒细胞浸润在2 d和5 d敏捷WT小鼠治疗。小鼠局部接受敏捷和CAM12 IP又一次重复的发现与MMP-8KO老鼠。这些结果表明,一些敏捷是介导的抗炎作用通过增加MMP-8表达式。威利期刊公司。

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