Department of Ophthalmology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.
The First School of Clinical Medicine, Anhui Medical University, Hefei, Anhui, China.
Ocul Immunol Inflamm. 2024 Dec;32(10):2449-2458. doi: 10.1080/09273948.2024.2409371. Epub 2024 Oct 1.
This study aims to investigate the role of Interleukin-37 (IL-37) in mouse models of dry eye.
Two murine models of dry eye were employed in this investigation. The evaluation of the anti-inflammatory impact of IL-37 (200 μl, 10 μg/ml) on dry eye mice involved intraperitoneal injections administered once daily for 7 days. Additionally, intraperitoneal injection of VO-Ohpic trihydrate (VO, 0.25 mg/kg) in dry eye mice was performed to investigate the role of PTEN in the IL-37 anti-inflammatory signaling pathway. Tear production was assessed using phenol red cotton thread, while corneal damage was examined through sodium fluorescein staining using a slit lamp. Histological alterations in the lacrimal gland were observed through H&E staining. PAS staining was used to assess conjunctival goblet cells. The levels of NFκB-P65, p-NFκB-P65, IL-1β, IL-6, TNF-α, CD3, AQP5, α-SMA and PTEN proteins were determined via Western blotting or immunofluorescence.
Following IL-37 treatment, both dry eye models exhibited reduced corneal fluorescence staining scores and enhanced tear production. In lacrimal gland, the expression of p-NFκB-P65, IL-1β, IL-6, CD3 and TNF-α was diminished, while PTEN, AQP5, α-SMA expression increased after IL-37 treatment in both dry eye mice. However, the intraperitoneal injection of VO significantly attenuated the anti-inflammatory effect of IL-37 on dry eye mice.
IL-37 emerges as an anti-inflammatory mediator within the lacrimal gland of dry eye mice, exerting its effects through the IL-37-PTEN-NFκB signaling pathway.
本研究旨在探讨白细胞介素-37（IL-37）在干眼症小鼠模型中的作用。
本研究采用了两种干眼症小鼠模型。通过腹腔注射 IL-37（200μl，10μg/ml），每日一次，连续 7 天，评估 IL-37 对干眼症小鼠的抗炎作用。此外，通过腹腔注射 VO-Ohpic 三水合物（VO，0.25mg/kg）在干眼症小鼠中研究 PTEN 在 IL-37 抗炎信号通路中的作用。使用苯酚红棉线评估泪液产生，使用裂隙灯通过荧光素钠染色评估角膜损伤。通过 H&E 染色观察泪腺的组织学改变。使用 PAS 染色评估结膜杯状细胞。通过 Western blot 或免疫荧光测定 NFκB-P65、p-NFκB-P65、IL-1β、IL-6、TNF-α、CD3、AQP5、α-SMA 和 PTEN 蛋白的水平。
IL-37 治疗后，两种干眼症模型的角膜荧光染色评分均降低，泪液产生增加。在泪腺中，p-NFκB-P65、IL-1β、IL-6、CD3 和 TNF-α 的表达减少，而 IL-37 治疗后干眼症小鼠的 PTEN、AQP5 和 α-SMA 表达增加。然而，腹腔注射 VO 显著减弱了 IL-37 对干眼症小鼠的抗炎作用。
IL-37 作为干眼症小鼠泪腺中的抗炎介质，通过 IL-37-PTEN-NFκB 信号通路发挥作用。
