不同浓度伏立康唑对人急性单核细胞白血病细胞株来源巨噬细胞免疫功能的影响  

Effects of different concentrations of voriconazole on THP-1-induced macrophage immune function

作　　者：滕国杰[1] 聂秀红[1] TENG Guojie;NIE Xiuhong(Department of respiratory and critical care medicine,Xuanwu Hospital Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院呼吸与危重症医学科,北京100053

出　　处：《中国真菌学杂志》2023年第5期385-390,共6页Chinese Journal of Mycology

摘　　要：目的探讨不同伏立康唑药物浓度对人急性单核细胞白血病细胞株(human acute monocytic leukemia cell line,THP-1细胞株)来源巨噬细胞免疫功能的影响。方法THP-1来源巨噬细胞中加入最终浓度为0、0.25、0.5、1、2、4、8、16、32、64μg/mL的伏立康唑,加入灭活烟曲霉菌液(inactivated Aspergillus fumigatus liquid,IAFL),培养箱孵育6 h。检测培养上清液中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)及白细胞介素-10(interleukin-10,IL-10)的浓度;流式细胞仪检测THP-1来源巨噬细胞膜表面Toll样受体-2(Toll like receptor-2,TLR2)、Toll样受体-4(Toll like receptor-4,TLR4)、树突状细胞相关C型凝集素-1(dendritic cell-associated C-type lectin-1,Dectin-1)的表达。结果加入浓度4~64μg/mL伏立康唑时,培养上清液中TNF-α、IL-1β的浓度较对照组(仅含THP-1来源巨噬细胞和灭活烟曲霉菌液)明显升高(P均<0.05),在伏立康唑的浓度16μg/mL和8μg/mL时,TNF-α和IL-1β浓度分别达到峰值。IL-10浓度在不同伏立康唑浓度组中均无显著性差异(P>0.05)。加入浓度1~64μg/mL伏立康唑时,巨噬细胞膜表面TLR2、TLR4、Dectin-1平均荧光强度(median fluorescence intensity,MFI)较灭活烟曲霉菌液对照组均明显升高(P<0.05)。在伏立康唑浓度为4μg/mL、4μg/mL、1μg/mL时,细胞膜表面TLR2、TLR4、Dectin-1的平均荧光强度分别达到峰值。结论在灭活烟曲霉菌液存在时,伏立康唑浓度在4~64μg/mL时可以刺激THP-1来源巨噬细胞TNF-α、IL-1β分泌明显增加,细胞膜表面TLR2、TLR4和Dectin-1的表达增强。但这种加强并不是随伏立康唑剂量增加而持续增高。Objective The aim of this study was to explore the effects of concentrations of voriconazole on the macrophages immune function induced by THP-1 cells.Methods Different concentrations of voriconazole were added to THP-1 induced macrophages,the final concentration of voriconazole was 0,0.25,0.5,1,2,4,8,16,32,64μg/mL,and the inactivated Aspergillus fumigatus liquid(IAFL)was added,incubate for 6 hours.Tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)concentration in the culture supernatant were detected.Flow cytometry was used to detect the expression of Toll like receptor-2(TLR2),Toll like receptor-4(TLR4),and dendritic cell-associated C-type lectin-1(Dectin-1)on the macrophages membrane surface.Result When the concentration of voriconazole was between 4 and 64μg/mL,the concentrations of TNF-αand IL-1βwere significantly higher than those of the control group(containing only THP-1-derived macrophages and inactivated Aspergillus fumigatus liquid)(P<0.05).The concentrations of TNF-αand IL-1βpeaked at voriconazole concentrations of 16μg/mL and 8μg/mL,respectively.There was no significant difference in IL-10 concentration among different voriconazole concentration groups(P all>0.05).When the concentration of voriconazole was 1-64μg/mL,the median fluorescence intensity of TLR2,TLR4,and Dectin-1 on the cell membrane surface was significantly higher than that of the IAFL control group(P<0.05).When voriconazole concentration was 4μg/mL,4μg/mL and 1μg/mL,the average fluorescence intensity of TLR2,TLR4 and Dectin-1 on the cell membrane surface reached the peak.Conclusion In the presence of IAFL,the secretion of TNF-αand IL-1βfrom macrophages induced by THP-1 could be stimulated by voriconazole.The expression of TLR2,TLR4 and dectin-1 on the surface of macrophage membrane was enhanced.However,the enhancement did not increase continuously with the increase of voriconazole dose.

关 键 词：伏立康唑 巨噬细胞 模式识别受体 细胞因子 

分 类 号：R978.5[医药卫生—药品]