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Erb-(IL10)2通过清除氧自由基改善辐射诱导的皮肤损伤。

Erb-(IL10)2 ameliorates radiation-induced skin injury through eliminate oxygen free radicals.

作者信息

Xu Jiahe, Zhu Jiaxing, Zhao Qi, Xue Jiao, Qin Songbing

机构信息

Department of Radiation Oncology First Affiliated Hospital of Soochow University Suzhou Jiangsu China.

出版信息

Precis Radiat Oncol. 2023 Jun 12;7(2):92-100. doi: 10.1002/pro6.1193. eCollection 2023 Jun.

Abstract

OBJECTIVE

Radiation-induced skin injury (RISI) remains a serious concern during radiotherapy. IL-10 is considered as an immune suppressive cytokine by inhibiting the secretion of the proinflammatory cytokines in cells. The aim of this study was to evaluate the protective role of Erb (IL10) 2 against ionizing radiation.

METHODS

We fused Interleukin 10 (IL-10) dimer onto an anti-epidermal growth factor receptor antibody Cetuximab (Erbitux) to form a new bispecific protein Erb-(IL10)2. The protective effect and biological activity of Erb-(IL10)2 was measured in model of RISI.

RESULTS

Under the condition of 20 Gy irradiation, surviving cells in the IR group decreased significantly compared with the non-IR group ( = 0.0021). The survival rates of HaCaT ( = 0.0038) and WS1 ( = 0.0003) cells were significantly increased after IL-10 treatment. The apoptosis rates of HaCaT ( = 0.0048) and WS1 ( = 0.0074) cells in the IL-10 group were significantly lower compared to the NC group. Under 20 Gy irradiation conditions, IL-10 fusion protein reduced the level of reactive oxygen in HaCaT ( = 0.0046) and WS1 (<0.0001) cells compared to the control group. Relatively normal granular mitochondrial morphology was observed in the IL-10 group after 20 Gy X-ray irradiation compared with the NC group. Ater 35 Gy electron radiation, the levels of reactive oxygen species in the skin tissue of C57/B6 mice injected with IL-10 fusion protein were significantly lower than those in the PBS group ( = 0.001). Compared with the PBS group and the other IL-10 groups, the group treated with 0.2 mg/kg IL-10 showed a significant decrease in MDA level ( = 0.0024). Compared with the PBS group, the thickness of the stratum corneum in groups treated with 0.05, 0.1 and 0.2 mg/kg IL-10 decreased, and the skin appendages were well-preserved. In the group treated with 0.2 mg/kg IL-10, the skin tissue structure was still relatively intact, and the masson staining area was smaller than that of the PBS group.

CONCLUSION

IL-10 plays a role in inhibiting radioactive fibrosis in radioactive skin injury. IL-10 has a protective effect on skin cell damage after ionizing radiation irradiation both in vitro and in vivo. Moreover, IL-10 plays a role in inhibiting radioactive fibrosis in radioactive skin injury.

摘要

目的

放射诱导的皮肤损伤(RISI)在放射治疗期间仍然是一个严重问题。白细胞介素10(IL-10)通过抑制细胞中促炎细胞因子的分泌被认为是一种免疫抑制细胞因子。本研究的目的是评估Erb(IL10)2对电离辐射的保护作用。

方法

我们将白细胞介素10(IL-10)二聚体与抗表皮生长因子受体抗体西妥昔单抗(爱必妥)融合,形成一种新的双特异性蛋白Erb-(IL10)2。在RISI模型中测量Erb-(IL10)2的保护作用和生物学活性。

结果

在20 Gy照射条件下,与未照射组相比,照射组存活细胞显著减少(P = 0.0021)。IL-10处理后,HaCaT细胞(P = 0.0038)和WS1细胞(P = 0.0003)的存活率显著增加。与阴性对照组相比,IL-10组HaCaT细胞(P = 0.0048)和WS1细胞(P = 0.0074)的凋亡率显著降低。在20 Gy照射条件下,与对照组相比,IL-10融合蛋白降低了HaCaT细胞(P = 0.0046)和WS1细胞(P<0.0001)中的活性氧水平。与阴性对照组相比,20 Gy X射线照射后IL-10组观察到相对正常的颗粒状线粒体形态。35 Gy电子辐射后,注射IL-10融合蛋白的C57/B6小鼠皮肤组织中的活性氧水平显著低于PBS组(P = 0.001)。与PBS组和其他IL-10组相比,用0.2 mg/kg IL-10处理的组丙二醛水平显著降低(P = 0.0024)。与PBS组相比,用0.05、0.1和0.2 mg/kg IL-10处理的组角质层厚度降低,皮肤附属器保存良好。在0.2 mg/kg IL-10处理的组中,皮肤组织结构仍然相对完整,Masson染色面积小于PBS组。

结论

IL-10在放射性皮肤损伤中对放射性纤维化起抑制作用。IL-10在体外和体内对电离辐射照射后的皮肤细胞损伤均具有保护作用。此外,IL-10在放射性皮肤损伤中对放射性纤维化起抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a5f/11935052/81e28d35777c/PRO6-7-92-g003.jpg

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