SENP3 缺失通过增加交替激活的巨噬细胞促进鼻黏膜炎症中的鼻息肉形成。
Loss of SENP3 mediated the formation of nasal polyps in nasal mucosal inflammation by increasing alternative activated macrophage.
机构信息
Otorhinolaryngology Department of Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Institutes of Medical Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
出版信息
Immun Inflamm Dis. 2023 Feb;11(2):e781. doi: 10.1002/iid3.781.
BACKGROUND AND AIM
Small ubiquitin-like modifier (SUMO)-specific protease (SENP)3 is a protease molecule that responds to reactive oxygen species (ROS) with high sensitivity. However, the role of ROS and SENP3 in the formation of nasal polyps (NPs) remains unclear. This study aimed to explore how SENP3 influenced the outcome of chronic rhinosinusitis (CRS) by altering macrophage function, that is, the formation of NPs.
METHODS
The alternative activation of macrophage (M2) was detected with CD68 CD206 in humans and CD206 in mice. The nasal mucosa of patients with CRS was tested using flow cytometry (CD68, CD80, and CD206) and triple-color immunofluorescence staining (CD68, CD206, and SENP3). The bone marrow-derived macrophages from SENP3 knockout and control mice were stimulated with interleukin (IL)-4 and IL-13 to analyze alternative macrophage polarization in vitro. An animal model of allergic rhinitis was constructed using SENP3 knockout mice. CD206 was detected by immunofluorescence staining. The thickening of eosinophil-infiltrated mucosa was detected by Luna staining.
RESULTS
The number of CD68 CD206 M2 increased in the nasal mucosa of patients with CRS with NP (CRSwNP) compared with patients with CRS without NP (CRSsNP), but with no significant difference between the groups. SENP3 knockout increased the polarization of F4/80 CD206 M2. Meanwhile, the number of CD206 M2 significantly increased in the allergic rhinitis model constructed using SENP3 knockout mice and controls, with a more obvious proliferation of the nasal mucosa.
CONCLUSION
Downregulation of SENP3 promotes the formation of nasal polyps mediated by increasing alternative activated macrophage in nasal mucosal inflammation.
背景与目的
小泛素样修饰酶（SUMO）特异性蛋白酶（SENP）3 是一种对活性氧（ROS）具有高灵敏度的蛋白酶分子。然而，ROS 和 SENP3 在鼻息肉（NP）形成中的作用尚不清楚。本研究旨在通过改变巨噬细胞功能（即 NP 的形成）来探讨 SENP3 如何影响慢性鼻-鼻窦炎（CRS）的结果。
方法
采用 CD68 CD206 在人类和 CD206 在小鼠中检测巨噬细胞（M2）的选择性激活。采用流式细胞术（CD68、CD80 和 CD206）和三色免疫荧光染色（CD68、CD206 和 SENP3）检测 CRS 患者的鼻黏膜。用白细胞介素（IL）-4 和 IL-13 刺激 SENP3 敲除和对照小鼠的骨髓来源巨噬细胞，在体外分析选择性巨噬细胞极化。用 SENP3 敲除小鼠构建变应性鼻炎动物模型。通过免疫荧光染色检测 CD206。通过 Luna 染色检测嗜酸性粒细胞浸润黏膜的增厚。
结果
与无 NP 的 CRS（CRSsNP）患者相比，伴有 NP 的 CRS（CRSwNP）患者鼻黏膜中 CD68 CD206 M2 的数量增加，但两组之间无显著差异。SENP3 敲除增加了 F4/80 CD206 M2 的极化。同时，在 SENP3 敲除小鼠和对照构建的变应性鼻炎模型中，CD206 M2 的数量明显增加，鼻黏膜增生更明显。
结论
SENP3 的下调通过增加鼻黏膜炎症中选择性激活的巨噬细胞促进鼻息肉的形成。
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