结膜 Toll 样受体 3 的表达在紫外线诱导翼状胬肉形成中起致病作用。

Conjunctival Expression of Toll-Like Receptor 3 Plays a Pathogenic Role in the Formation of Ultraviolet Light-Induced Pterygium.

机构信息

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Department of Ophthalmology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

Invest Ophthalmol Vis Sci. 2021 Aug 2;62(10):6. doi: 10.1167/iovs.62.10.6.

DOI:10.1167/iovs.62.10.6

PMID:34369985

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8354036/

Abstract

PURPOSE

Toll-like receptor 3 (TLR3), as a damage-associated molecular pattern sensor, can detect self-RNA released from necrotic cells induced by ultraviolet B (UVB) radiation exposure. Pterygium formation is believed to be a tumorigenesis-like process induced by UVB exposure. In this study, we aimed to investigate the expression pattern of TLR3 in pterygium specimens and cultured pterygial epithelial cells (PECs).

METHODS

Human pterygium and ipsilateral pterygium-free conjunctiva from the same patients were used in this study. The expression of TLR3 and nuclear factor-kappa B (NF-κB) was investigated in these specimens. PECs were exposed to UVB radiation to determine the effect of UVB on the expression of TLR3 and the activation of NF-κB.

RESULTS

The immunofluorescence study showed stronger TLR3 expression in superficial epithelial cells in the pterygial epithelium in comparison with the normal conjunctival epithelium. The expression of TLR3 decreased in intensity from the superficial epithelium toward the basal cell layer, implying a correlation between UVB exposure and TLR3 expression. Differential TLR3 expression patterns in pterygial and conjunctival tissues were also found in quantitative PCR analyses. PECs after UVB irradiation had higher protein levels of TLR3 and phospho-NF-κB than those of the PECs without irradiation. Immunofluorescence studies showed that UVB irradiation induced the nuclear translocation of NF-κB in the PECs. In PECs with the targeted TLR3 gene silencing, the expression of phospho-NF-κB was not induced by UVB irradiation.

CONCLUSIONS

Our results indicate that UVB exposure, TLR3 expression, and NF-κB activation may be a critical sequence that leads to the formation of pterygium.

摘要

目的

Toll 样受体 3（TLR3）作为一种损伤相关分子模式传感器，可以检测到由紫外线 B（UVB）辐射暴露引起的坏死细胞释放的自身 RNA。翼状胬肉的形成被认为是一种由 UVB 暴露引起的肿瘤样过程。在这项研究中，我们旨在研究 TLR3 在翼状胬肉标本和培养的翼状胬肉上皮细胞（PECs）中的表达模式。

方法

本研究使用了来自同一患者的人翼状胬肉和同侧无翼状胬肉的结膜。研究了这些标本中 TLR3 和核因子-κB（NF-κB）的表达。将 PECs 暴露于 UVB 辐射下，以确定 UVB 对 TLR3 表达和 NF-κB 激活的影响。

结果

免疫荧光研究表明，与正常结膜上皮相比，翼状胬状上皮的浅层上皮细胞中 TLR3 的表达更强。TLR3 的表达强度从浅层上皮向基底细胞层逐渐减弱，提示 UVB 暴露与 TLR3 表达之间存在相关性。定量 PCR 分析也发现了翼状胬状和结膜组织中 TLR3 表达模式的差异。与未照射的 PECs 相比，经 UVB 照射后的 PECs 中 TLR3 和磷酸化 NF-κB 的蛋白水平更高。免疫荧光研究表明，UVB 照射诱导了 PECs 中 NF-κB 的核转位。在 TLR3 基因靶向沉默的 PECs 中，UVB 照射不会诱导磷酸化 NF-κB 的表达。