Favorable effects of trehalose on the development of UVB-mediated antioxidant/pro-oxidant imbalance in the corneal epithelium, proinflammatory cytokine and matrix metalloproteinase induction, and heat shock protein 70 expression
Favorable effects of trehalose on the development of UVB-mediated antioxidant/pro-oxidant imbalance in the corneal epithelium, proinflammatory cytokine and matrix metalloproteinase induction, and heat shock protein 70 expression
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DOI：
10.1007/s00417-011-1676-y
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发表时间：
2011-08-01
影响因子：
2.7
通讯作者：
Luyckx, Jacques
中科院分区：
文献类型：
--
作者：
Cejkova, Jitka;Ardan, Taras;Luyckx, Jacques
海藻糖是葡萄糖的一种非还原性二糖，当细胞暴露于应激条件下时，作为应激反应因子合成。在角膜中，氧化应激在UVB射线引起的急性角膜炎症反应、光性角膜炎的发展中起关键作用。我们以前发现，海藻糖减少UVB诱导的氧化作用的形成细胞毒性过氧亚硝酸盐，凋亡角膜上皮细胞死亡和角膜光学的变化。本研究的目的是检查海藻糖是否可能抑制UVB介导的促炎细胞因子和基质金属蛋白酶诱导以及角膜上皮中抗氧化剂/促氧化剂失衡的发展，这些变化先前被发现与急性角膜UVB诱导的炎症密切相关。用波长为312 nm，剂量为0.5 J/cm ~ 2的UVB照射新西兰白色兔角膜，连续4 d，观察UVB对角膜热休克蛋白70表达的影响。在照射期间，将海藻糖滴剂应用于右眼，将缓冲盐水应用于左眼。照射结束后一天，处死动物，用化学方法检测角膜抗氧化酶的表达（过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶）、促氧化剂黄嘌呤氧化还原酶/黄嘌呤氧化酶、促炎细胞因子（白细胞介素-6，白细胞介素-8），基质金属蛋白酶-9和热休克蛋白70。在UVB照射期间缓冲盐水处理后，抗氧化剂/促氧化剂失衡出现在角膜上皮中：抗氧化酶的表达高度降低，而促氧化剂黄嘌呤氧化酶的表达增加。在UVB照射的角膜上皮中发现促炎细胞因子、基质金属蛋白酶和热休克蛋白70的显著表达。海藻糖的应用显着抑制上述所有UVB诱导的角膜干扰。海藻糖有利地影响UVB射线引起的角膜氧化损伤。海藻糖抑制促炎细胞因子诱导。研究表明，促炎细胞因子的抑制强烈有助于减少UVB照射的角膜上皮中基质金属蛋白酶和黄嘌呤氧化酶的表达，并减少抗氧化剂/促氧化剂失衡的发展。热休克蛋白70的过度表达，发现在UVB照射角膜后缓冲盐水治疗后，海藻糖应用减少。
Trehalose, a nonreducing disaccharide of glucose, is synthesized as a stress response factor when cells are exposed to stressful conditions. In the cornea, oxidative stress plays the key role in the development of acute corneal inflammatory response to UVB rays, photokeratitis. We found previously that trehalose reduced UVB-induced oxidative effects on the formation of cytotoxic peroxynitrite, apoptotic corneal epithelial cell death and changes in corneal optics. The aim of the present study was to examine whether trehalose might inhibit UVB-mediated proinflammatory cytokine and matrix metalloproteinase induction and the development of an antioxidant/pro-oxidant imbalance in the corneal epithelium, changes found previously to be strongly involved in the acute corneal UVB-induced inflammation. The expression of heat shock protein 70 as a potential biomarker for corneal UVB-induced damage was also examined.The corneas of New Zealand white rabbits were irradiated with UVB rays, 312 nm, daily dose of 0.5 J/cm(2) for 4 days. During the irradiation, trehalose drops were applied on the right eye and buffered saline on the left eye. One day after the end of irradiations, the animals were killed and the corneas examined immunohistochemically for the expression of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), pro-oxidant xanthine oxidoreductase/xanthine oxidase, proinflammatory cytokines (interleukin-6, interleukin-8), matrix metalloproteinase-9 and heat shock protein 70.After buffered saline treatment during UVB irradiation, an antioxidant/pro-oxidant imbalance appeared in the corneal epithelium: The expression of antioxidant enzymes was highly reduced, whereas the expression of pro-oxidant xanthine oxidase was increased. The pronounced expression of pro-inflammatory cytokines, matrix metalloproteinase and heat shock protein 70 was found in the UVB-irradiated corneal epithelium. Trehalose application significantly suppressed all the above-mentioned UVB-induced corneal disturbances.Trehalose favorably influenced the oxidative damage of the cornea caused by UVB rays. Trehalose suppressed proinflammatory cytokine induction. It is suggested that suppression of proinflammatory cytokines contributed strongly to reduced matrix metalloproteinase and xanthine oxidase expression in the UVB-irradiated corneal epithelium and to the decreased development of an antioxidant/pro-oxidant imbalance. The overexpression of heat shock protein 70 found in UVB-irradiated cornea after buffered saline treatment was reduced after trehalose application.