肿瘤坏死因子-α 诱导蛋白 3 可能是 TLR4 在视网膜血管中激活炎症小体的关键。
TNFAIP3 may be key to TLR4-activation of the inflammasome in the retinal vasculature.
机构信息
Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
出版信息
Exp Eye Res. 2022 Jul;220:109108. doi: 10.1016/j.exer.2022.109108. Epub 2022 May 11.
The goal of these studies were to determine whether tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) regulated toll-like receptor 4 (TLR4) actions on the NOD-like receptor protein 3 (NLRP3) inflammasome. Western blotting was done on retinal lysates from TLR4 floxed and endothelial cell specific TLR4 knockout mice for TNFAIP3, TLR4, and NLRP3 pathway proteins. Retinal endothelial cells (REC) were grown in normal (5 mM) and high glucose (25 mM) and treated with TNFAIP3 siRNA, followed by Western blotting for TLR4 and NLRP3 pathway proteins. Loss of TLR4 in endothelial cells increased TNFAIP3 levels, while decreasing NLRP3 pathway proteins. High glucose culturing conditions increased TLR4 and NLRP3 proteins, which were also increased by TNFAIP3 siRNA. Data demonstrate that TLR4 regulates NLRP3 pathway proteins. TNFAIP3 can regulate TLR4 and the NLRP3 pathway. TNFAIP3 may offer a new target for therapeutic development against retinal inflammation.
这些研究的目的是确定肿瘤坏死因子-α诱导蛋白 3（TNFAIP3）是否调节 Toll 样受体 4（TLR4）对 NOD 样受体蛋白 3（NLRP3）炎症小体的作用。对 TLR4 基因敲除和内皮细胞特异性 TLR4 基因敲除小鼠的视网膜裂解物进行 Western 印迹分析，以检测 TNFAIP3、TLR4 和 NLRP3 途径蛋白。将视网膜内皮细胞（REC）在正常（5mM）和高糖（25mM）条件下培养，并进行 TNFAIP3 siRNA 处理，然后进行 Western 印迹分析，以检测 TLR4 和 NLRP3 途径蛋白。内皮细胞中 TLR4 的缺失增加了 TNFAIP3 的水平，同时降低了 NLRP3 途径蛋白。高糖培养条件增加了 TLR4 和 NLRP3 蛋白，而 TNFAIP3 siRNA 也增加了这些蛋白。这些数据表明，TLR4 调节 NLRP3 途径蛋白。TNFAIP3 可以调节 TLR4 和 NLRP3 途径。TNFAIP3 可能为治疗视网膜炎症提供新的靶点。
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