Abstract：
BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive.
OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP.
METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages.
RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis.
CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.
OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP.
METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages.
RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis.
CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.
摘要：
背景：先前的研究提示，在慢性鼻窦炎伴鼻息肉（CRSwNP）中，巨噬细胞的局部M2极化促进粘膜水肿并加剧Th2型炎症。然而,M2巨噬细胞和内在调节因子在CRS发展中的特定致病作用仍然难以捉摸。
目的：我们认为研究SIRT5在M2巨噬细胞极化中的调节作用及其对CRSwNP发展的潜在贡献。
方法：进行RT-qPCR和Western印迹分析，以检查从CRS和对照组获得的鼻窦粘膜样品中SIRT5和M2巨噬细胞标志物的表达水平。采用野生型和Sirt5基因敲除小鼠建立Th2炎症的鼻息肉模型，研究巨噬细胞SIRT5对疾病发展的影响。此外，进行了体外实验以阐明SIRT5在M2巨噬细胞极化中的调节作用。
结果：临床研究表明，SIRT5在嗜酸性息肉中高表达，并与M2巨噬细胞标志物呈正相关。SIRT5在M2巨噬细胞中的表达被发现有助于疾病的发展，在Sirt5缺乏症小鼠中受损。机械上,SIRT5显示通过促进谷氨酰胺分解增强巨噬细胞的替代极化。
结论：SIRT5通过支持巨噬细胞的替代极化在促进CRSwNP的发展中起着至关重要的作用，因此为CRSwNP干预提供了潜在的靶标。
目的：我们认为研究SIRT5在M2巨噬细胞极化中的调节作用及其对CRSwNP发展的潜在贡献。
方法：进行RT-qPCR和Western印迹分析，以检查从CRS和对照组获得的鼻窦粘膜样品中SIRT5和M2巨噬细胞标志物的表达水平。采用野生型和Sirt5基因敲除小鼠建立Th2炎症的鼻息肉模型，研究巨噬细胞SIRT5对疾病发展的影响。此外，进行了体外实验以阐明SIRT5在M2巨噬细胞极化中的调节作用。
结果：临床研究表明，SIRT5在嗜酸性息肉中高表达，并与M2巨噬细胞标志物呈正相关。SIRT5在M2巨噬细胞中的表达被发现有助于疾病的发展，在Sirt5缺乏症小鼠中受损。机械上,SIRT5显示通过促进谷氨酰胺分解增强巨噬细胞的替代极化。
结论：SIRT5通过支持巨噬细胞的替代极化在促进CRSwNP的发展中起着至关重要的作用，因此为CRSwNP干预提供了潜在的靶标。
