TNFAIP3 is anti-inflammatory in the retinal vasculature.

IF 1.8 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Vision Pub Date : 2022-01-01

Li Liu, Youde Jiang, Jena J Steinle

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引用次数: 0

Abstract

Purpose: To determine whether tumor necrosis factor alpha-induced protein 3 (TNFAIP3) regulates inflammatory and permeability proteins in the retinal vasculature.

Methods: We used retinal lysates from type 1 diabetic mice and endothelial cell-specific exchange protein for cAMP 1 (Epac1) knockout mice to determine the protein levels of TNFAIP3. We also treated retinal endothelial cells (RECs) in normal (5 mM) and high (25 mM) glucose with an Epac1 agonist or with TNFAIP3 siRNA. We performed western blotting for TNFAIP3 and inflammatory and permeability proteins after treatment. TNFAIP3 siRNA was used only in cells grown in high glucose. Immunostaining was performed for localization of ZO-1 and tight junction protein 1.

Results: TNFAIP3 was reduced in the diabetic retinas and the retinas of the Epac1 conditional knockout mice. The Epac1 agonist increased TNFAIP3 levels in RECs grown in high glucose. Reduction of TNFAIP3 with siRNA led to increased levels of tumor necrosis factor alpha (TNFα) and phosphorylation of nuclear factor kappa beta (NF-kB), while decreasing occludin and zonula occludens 1 (ZO-1) protein levels and inhibitory kappa beta kinase (IkB) phosphorylation. Tumor receptor-associated factor 6 (TRAF6) levels were increased above high glucose levels.

Conclusions: TNFAIP3 serves as an anti-inflammatory factor in the retinal vasculature. Epac1 regulates TNFAIP3. TNFAIP3 may offer a new mechanism for regulating inflammation and permeability in the retinal vasculature.

本刊更多论文

TNFAIP3在视网膜血管中具有抗炎作用。

目的:探讨肿瘤坏死因子α诱导蛋白3 (TNFAIP3)是否调控视网膜血管中的炎症和通透性蛋白。方法:我们使用1型糖尿病小鼠的视网膜裂解液和cAMP 1 (Epac1)敲除小鼠的内皮细胞特异性交换蛋白来测定TNFAIP3的蛋白水平。我们还使用Epac1激动剂或TNFAIP3 siRNA处理正常(5 mM)和高(25 mM)葡萄糖的视网膜内皮细胞(RECs)。治疗后对TNFAIP3、炎症和通透性蛋白进行western blotting检测。TNFAIP3 siRNA仅在高糖生长的细胞中使用。免疫染色定位ZO-1和紧密连接蛋白1。结果:糖尿病视网膜和Epac1条件敲除小鼠视网膜中TNFAIP3均降低。Epac1激动剂可提高高糖条件下生长的RECs中TNFAIP3水平。用siRNA减少TNFAIP3导致肿瘤坏死因子α (TNFα)水平和核因子κ β (NF-kB)磷酸化水平升高，而occludin和ZO-1蛋白水平降低，抑制κ β激酶(IkB)磷酸化。肿瘤受体相关因子6 (TRAF6)水平高于高血糖水平。结论:TNFAIP3在视网膜血管中发挥抗炎因子的作用。Epac1调控TNFAIP3。TNFAIP3可能为调节视网膜血管的炎症和通透性提供了一种新的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Vision 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.