Han S J, Min H J, Yoon S C, Ko E A, Park S J, Yoon J-H, Shin J-S, Seo K Y
Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Otorhinolaryngology - Head and Neck Surgery, Chung-Ang University College of Medicine, Seoul, Korea.
Cell Death Dis. 2015 Aug 27;6(8):e1863. doi: 10.1038/cddis.2015.199.
High-mobility group box 1 (HMGB1) functions as a transcription-enhancing nuclear protein as well as a crucial cytokine that regulates inflammation. This study demonstrated that secretion of HMGB1 due to ultraviolet (UV) radiation inducing ocular surface inflammation-mediated reactive oxygen species (ROS) production. After treating conjunctival epithelial cells with UV radiation, HMGB1 was translocated from the nucleus to the cytoplasm and then eventually to the extracellular space. HMGB1 played a crucial role in UV-induced conjunctival neutrophil infiltration, which subsided when mice were pretreated with the HMGB1 inhibitors soluble receptor for advanced glycation endproducts (sRAGEs) and HMGB1 A box protein. In case of using ROS quencher, there was decrease in UV-induced HMGB1 secretion in conjunctival epithelial cells and mice. Considering that UV-induced chronic inflammation causes ocular surface change as pterygium, we have confirmed high HMGB1 translocation and ROS expression in human pterygium. Our findings therefore revealed a previously unknown mechanism of UV-induced ocular inflammation related to ROS and HMGB1 suggesting a new medical therapeutic target.
高迁移率族蛋白B1（HMGB1）作为一种增强转录的核蛋白以及一种调节炎症的关键细胞因子发挥作用。本研究表明，紫外线（UV）辐射诱导眼表炎症介导的活性氧（ROS）产生会导致HMGB1分泌。用UV辐射处理结膜上皮细胞后，HMGB1从细胞核转移至细胞质，最终进入细胞外空间。HMGB1在UV诱导的结膜中性粒细胞浸润中起关键作用，当用HMGB1抑制剂晚期糖基化终产物可溶性受体（sRAGEs）和HMGB1 A盒蛋白对小鼠进行预处理时，这种浸润会减轻。在使用ROS淬灭剂的情况下，结膜上皮细胞和小鼠中UV诱导的HMGB1分泌减少。鉴于UV诱导的慢性炎症会导致眼表出现如翼状胬肉等变化，我们已证实在人翼状胬肉中存在高HMGB1转移和ROS表达。因此，我们的研究结果揭示了一种先前未知的与ROS和HMGB1相关的UV诱导眼内炎症机制，提示了一个新的医学治疗靶点。
