Macular fibrosis is a vital obstacle of vision acuity improvement of age-related macular degeneration patients. This study was to investigate the effects of interleukin 2 (IL-2) on epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and transforming growth factor β2 (TGF-β2) expression in retinal pigment epithelial (RPE) cells. 10 μg/L IL-2 was used to induce fibrosis in RPE cells for various times. Western blot was used to detect the EMT marker α-smooth muscle actin (α-SMA), ECM markers fibronectin (Fn) and type 1 collagen (COL-1), TGF-β2, and the activation of the JAK/STAT3 and NF-κB signaling pathway. Furthermore, JAK/STAT3 and NF-κB signaling pathways were specifically blocked by WP1066 or BAY11-7082, respectively, and the expression of α-SMA, COL-1, Fn and TGF-β2 protein were detected. Wound healing and Transwell assays were used to measure cell migration ability of IL-2 with or without WP1066 or BAY11-7082. After induction of IL-2, the expressions of Fn, COL-1, TGF-β2 protein were significantly increased, and this effect was correlated with IL-2 treatment duration, while α-SMA protein expression did not change significantly. Both WP1066 and BAY11-7082 could effectively downregulate the expression of Fn, COL-1 and TGF-β2 induced by IL-2. What's more, both NF-κB and JAK/STAT3 inhibitors could suppress the activation of the other signaling pathway. Additionally, JAK/STAT3 inhibitor WP1066 and NF-κB inhibitor BAY 11-7082 could obviously decrease RPE cells migration capability induced by IL-2. IL-2 promotes cell migration, ECM synthesis and TGF-β2 expression in RPE cells via JAK/STAT3 and NF-κB signaling pathways, which may play an important role in proliferative vitreoretinopathy.

中文翻译：

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Interleukin-2诱导视网膜色素上皮细胞中的细胞外基质合成和TGF-β2表达。

黄斑纤维化是与年龄有关的黄斑变性患者视力提高的重要障碍。本研究旨在研究白介素2（IL-2）对视网膜色素上皮（RPE）细胞上皮-间质转化（EMT），细胞外基质（ECM）合成和转化生长因子β2（TGF-β2）表达的影响。10μg/ L IL-2用于诱导RPE细胞纤维化不同时间。Western blot检测EMT标记α-平滑肌肌动蛋白（α-SMA），ECM标记纤连蛋白（Fn）和1型胶原（COL-1），TGF-β2以及JAK / STAT3和NF的激活-κB信号通路。此外，WP1066或BAY11-7082分别特异性阻断JAK / STAT3和NF-κB信号通路，并检测α-SMA，COL-1，Fn和TGF-β2蛋白的表达。伤口愈合和Transwell分析用于测量有或没有WP1066或BAY11-7082的IL-2的细胞迁移能力。诱导IL-2后，Fn，COL-1，TGF-β2蛋白的表达显着升高，且此效应与IL-2治疗时间有关，而α-SMA蛋白表达无明显变化。WP1066和BAY11-7082均可有效下调IL-2诱导的Fn，COL-1和TGF-β2的表达。而且，NF-κB和JAK / STAT3抑制剂均可抑制其他信号通路的激活。此外，JAK / STAT3抑制剂WP1066和NF-κB抑制剂BAY 11-7082可以明显降低IL-2诱导的RPE细胞迁移能力。IL-2通过JAK / STAT3和NF-κB信号通路促进RPE细胞中的细胞迁移，ECM合成和TGF-β2表达，