利福平格拉斯特抑制 Th1 介导的干燥性角膜结膜炎。
Suppression of Th1-Mediated Keratoconjunctivitis Sicca by Lifitegrast.
机构信息
Department of Ophthalmology, Baylor College of Medicine , Houston, Texas.
出版信息
J Ocul Pharmacol Ther. 2018 Sep;34(7):543-549. doi: 10.1089/jop.2018.0047. Epub 2018 Jun 29.
Abstract
PURPOSE
Increased interferon gamma (IFN-γ) expression in dry eye causes ocular surface epithelial disease termed keratoconjunctivitis sicca (KCS). The purpose of this study was to investigated the effects of the LFA-1 antagonist, lifitegrast, in a mouse desiccating stress (DS) dry eye model that develops KCS similar to Sjögren syndrome.
METHODS
Mice were treated with vehicle or lifitegrast twice daily for 5 days and expression of Th1 family genes (IFN-γ, CXCL9, and CXCL11) was evaluated by real-time polymerase chain reaction. Cornea barrier function was assessed by Oregon Green dextran staining and goblet cell number and area were measured.
RESULTS
Compared to the vehicle-treated group, the lifitegrast-treated group had significantly lower expression of Th1 family genes, less corneal barrier disruption, and greater conjunctival goblet cell density/area.
CONCLUSIONS
These findings indicate that lifitegrast inhibits DS-induced IFN-γ expression and KCS. This suggests that ICAM-LFA-1 signaling is involved with generation of Th1 inflammation in KCS.
摘要
目的
干眼症中干扰素 γ（IFN-γ）表达增加会导致眼表面上皮疾病，称为干燥性角结膜炎（KCS）。本研究旨在研究 LFA-1 拮抗剂，lifitegrast，在一种类似于干燥综合征的 KCS 发展的小鼠干燥应激（DS）干眼症模型中的作用。
方法
小鼠用载体或 lifitegrast 每日两次处理 5 天，并通过实时聚合酶链反应评估 Th1 家族基因（IFN-γ、CXCL9 和 CXCL11）的表达。通过 Oregon Green 葡聚糖染色评估角膜屏障功能，并测量杯状细胞数量和面积。
结果
与载体处理组相比，lifitegrast 处理组 Th1 家族基因的表达明显降低，角膜屏障破坏减少，结膜杯状细胞密度/面积增加。
结论
这些发现表明 lifitegrast 抑制 DS 诱导的 IFN-γ 表达和 KCS。这表明 ICAM-LFA-1 信号参与了 KCS 中 Th1 炎症的产生。
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