Effect of medium and low doses X-ray irradiation on polarization type changes of tumor associated macrophages
10.3969/j.issn.1000-484X.2024.12.001
- VernacularTitle:中低剂量X射线照射对肿瘤相关巨噬细胞极化类型改变的影响研究
- Author:
Chaonan SUN
1
;
Yuxin LIU
;
Yunyun CHENG
;
Yuchen WU
;
Jiguo LIN
;
Yuyao WANG
;
Gang ZHAO
Author Information
1. 吉林大学公共卫生学院,国家卫生健康委员会放射生物学重点实验室,长春 130021
- Keywords:
X-ray;
Tumor associated macrophages;
Polarization;
Pathway
- From:
Chinese Journal of Immunology
2024;40(12):2465-2470,2477
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore effects and mechanisms of medium and low doses X-ray irradiation on polarization type changes of tumor associated macrophages(TAMs).Methods:Mouse RAW264.7 macrophage line was cultured with supernatant of 4T1 tumor cell culture(4T1-TCS)of mouse breast cancer,and induced to M2 TAMs.On this basis,medium and low doses X-ray irra-diation was conducted,and NO was detected by Griess method,CD86 and CD206 were detected by flow cytometry.ELISA was use to detect cytokines IL-10 and IL-12p70,immunofluorescence was use to detect iNOS and Arg-1.Western blot was used to detect polariza-tion related pathway proteins,and whether medium and low doses of radiation could alter polarization type of TAMs was observed.Results:4T1-TCS induced TAM had decreasing NO secretion and increasing CD206 and Arg-1 expressions,iNOS expression was decreased;with low doses irradiation(0.075 Gy,0.5 Gy,1 Gy)of TCS-TAM,compared with non irradiation group,NO secretion,expressions of CD86,CD206,Arg-1 and iNOS showed no significant changes;medium doses(2 Gy,4 Gy,6 Gy)of irradiation on TCS-TAM resulted in increased secretion of NO,and flow cytometry results showed increased expressions of CD86,decreased CD206 expression;immunofluorescence results showed an increase in iNOS expression and a decrease in Arg-1 expression in cells;ELISA results showed an increase in secretion of IL-12p70 by cells and a decrease in secretion of IL-10.Western blot results showed that NOX2,ATMS1981*,IRF5 proteins expressions were increased.Conclusion:4T1-TCS can successfully induce macrophage RAW264.7 polarize into M2 phenotype,while low dose irradiation has no significant effect on polarization phenotype of TCS-TAM.Medium dose irradiation can induce TCS-TAM polarization into M1 phenotype that inhibits tumor growth,and reversal mechanism of polarization may be related to IRF5 pathway.