Inhibiting NF-κB Signaling Activation Reduces Retinal Neovascularization by Promoting a Polarization Shift in Macrophages
| Autor: | Yixuan Yao, Jikui Shen, Bing Xie, Xi Shen, Yiyun Yao, Xiuping Chen, Ailing Sui, Yanji Zhu, Yujuan Cai, Anna M. Demetriades |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Proline Blotting Western Macrophage polarization M1 Retinal Neovascularization Real-Time Polymerase Chain Reaction Retina NF-κB Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Thiocarbamates medicine Animals Macrophage Phosphorylation Fluorescent Antibody Technique Indirect Chemistry Macrophages NF-kappa B Transcription Factor RelA Retinal Macrophage Activation Flow Cytometry eye diseases I-kappa B Kinase Cell biology Mice Inbred C57BL Oxygen Blot Disease Models Animal IκBα 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Intravitreal Injections Signal transduction M2 macrophage polarization Signal Transduction |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| DOI: | 10.1167/iovs.61.6.4 |
| Popis: | Purpose Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling is involved in regulating tumor angiogenesis and metastasis; however, the exact mechanism of action in retinal neovascularization (RNV) remains unclear. The purpose of this study was to determine the role and underlying mechanism of NF-κB in regulating RNV in retinal neovascularization mice. Methods Expression levels of NF-κB signaling were detected by immunofluorescence staining and western blotting in retinas of oxygen-induced retinopathy (OIR) mice. OIR mice were treated with either pyrrolidinedithiocarbamate (PDTC), a NF-κB signaling inhibitor, or PBS, and retinal flat-mounts were performed to quantify the area of RNV and the recruitment of retinal macrophages by immunofluorescence staining. Macrophage polarization detected by flow cytometric analysis and the expression of macrophage polarization-associated genes were evaluated by immunofluorescence staining, quantitative RT-PCR, and western blotting. Results Expression levels of phosphorylated IκBα (p-IκBα) and p-p65 increased in OIR mice. Inhibiting NF-κB signaling activation by PDTC significantly reduced RNV. After treatment with PDTC, a reduction in the quantity of macrophages was observed: M1 polarized macrophages decreased, and M2 polarized macrophages increased; the expression of M1 macrophage-associated cytokines decreased and M2 macrophage-associated cytokines increased in the retinas of OIR mice. Conclusions Blocking activation of NF-κB signaling reduces RNV by promoting polarization of M1 macrophages to M2 macrophages in OIR mice. |
| Databáze: | OpenAIRE |
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