IL-8 通过 CXCR1/2-NF-κB-RhoA 信号通路下调 E-钙黏蛋白和 ZO-1 的表达，促进晶状体囊残余细胞的迁移。

IL-8 promotes lens capsular residual cells migration by down-regulates expression of E-cadherin and ZO-1 via the CXCR1/2-NF-κB-RhoA signal pathway.

机构信息

Laboratory of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Laboratory of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Beijing Tsinghua Changgeng Hospital, Beijing, China.

出版信息

Int Immunopharmacol. 2024 Dec 5;142(Pt A):113074. doi: 10.1016/j.intimp.2024.113074. Epub 2024 Sep 7.

DOI:10.1016/j.intimp.2024.113074

PMID:39244903

Abstract

BACKGROUND

Posterior capsular opacification is a major complication following cataract surgery, marked by proliferation, migration, epithelial-mesenchymal transition, and fibrosis of residual epithelial cells. Various inflammatory cytokines are upregulated and contribute to the development of posterior capsular opacification. The effect of interleukin-8 on residual epithelial cells has not been fully determined.

METHODS

Aqueous humor and anterior capsules samples were collected from cataract surgery. Capsular bags from rats and pigs were cultured in DMEM media. Protein and mRNA expressions were measured using immunoblot and qPCR. Cell migration was assessed using the transwell assay.

RESULTS

Interleukin-8 is an early inflammatory factor secreted by residual lens epithelial cells. Migration of lens epithelial cells in aqueous humor positively correlates with interleukin-8 levels, and this effect is inhibited by the receptors of interleukin-8 CXCR1/2 blocker Reparaxin. The expression of tight-junction protein ZO-1 and cell-adhesion protein E-cadherin were down-regulated by administrating interleukin-8, and cell migration of both SRA01/04 cell line in vitro and capsular residual epithelial cells ex vivo were up-regulated via activating RhoA expression and RhoA/GTPase activity. The loss-of- function studies demonstrate that interleukin-8 binding to its receptor CXCR1/2 activates NF-κB/p65, which then turns on the RhoA's expression and RhoA/GTPase activity, and RhoA-modulated the downexpression of E-cadherin and ZO-1 and the increase of cell migration.

CONCLUSIONS

The upregulation in interleukin-8 occurs early in posterior capsular opacification and contributes to down-regulating tight-junctions among epithelial cells and elevates cell migration via the CXCR1/2-NF-κB-RhoA signaling pathway. These demonstrated that interleukin-8 could be a potential target for preventing posterior capsular opacification.

摘要

背景

后囊混浊是白内障手术后的主要并发症，其特征为残余的上皮细胞增殖、迁移、上皮-间充质转化和纤维化。各种炎症细胞因子上调，并有助于后囊混浊的发展。白细胞介素-8对残余上皮细胞的影响尚未完全确定。

方法

收集白内障手术后的房水和前囊样本。用 DMEM 培养基培养大鼠和猪的囊袋。使用免疫印迹和 qPCR 测量蛋白和 mRNA 表达。使用 Transwell 测定法评估细胞迁移。

结果

白细胞介素-8是残余晶状体上皮细胞分泌的早期炎症因子。房水中的晶状体上皮细胞迁移与白细胞介素-8水平呈正相关，而这种作用被白细胞介素-8受体 CXCR1/2 阻断剂 Reparaxin 抑制。紧密连接蛋白 ZO-1 和细胞黏附蛋白 E-钙黏蛋白的表达下调，通过激活 RhoA 表达和 RhoA/GTPase 活性，上调体外 SRA01/04 细胞系和囊残余上皮细胞的细胞迁移。功能丧失研究表明，白细胞介素-8与其受体 CXCR1/2 结合，激活 NF-κB/p65，从而开启 RhoA 的表达和 RhoA/GTPase 活性，RhoA 调节 E-钙黏蛋白和 ZO-1 的下调以及细胞迁移的增加。