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M2-like polarization of THP-1 monocyte-derived macrophages under chronic iron overload.
Annals of Hematology ( IF 3.5 ) Pub Date : 2020-02-01 , DOI: 10.1007/s00277-020-03916-8
Jun-Kai Kao,Shih-Chung Wang,Li-Wei Ho,Shi-Wei Huang,Cheng-Han Lee,Ming-Sheng Lee,Rei-Cheng Yang,Jeng-Jer Shieh

Macrophages are characterized by phenotypical and functional heterogeneity. In different microenvironments, macrophages can polarize into two types: classically activated macrophages (M1) or alternatively activated macrophages (M2). M1 macrophages are a well-known bacteriostatic macrophage, and conversely, M2 macrophages may play an important role in tumor growth and tissue remodeling. M1 macrophages have been reported to have high intracellular iron stores, while M2 macrophages contain lower intracellular iron. It has been well-described that disturbances of iron homeostasis are associated with altered immune function. Thus, it is important to investigate if chronic iron overload is capable of polarizing macrophages. Human monocytic leukemia THP-1 cells were maintained in culture medium that contained 100 μM ferrous sulfate heptahydrate (FeSO4) (I-THP-1) and differentiated into THP-1-derived macrophages (I-TDMs) by induction with phorbol 12-myristate 13-acetate (PMA). We characterized that I-TDMs not only enhanced the surface expression of CD163 and CD206 but also increased arginase and decreased iNOS protein expression. I-TDMs enhanced pSTAT6 expression and decreased pSTAT1 and NF-κB expressions. Furthermore, the gene expression profile of I-TDMs was comparable with M2 macrophages by performing human oligonucleotide DNA microarray analysis. Finally, functional assays demonstrated I-TDMs secreted higher levels of IL-10 but not M1 cytokines. Additionally, the conditional medium of I-TDMs had enhanced migration and increased invasion of A375 melanoma cells which was similar to the characteristics of tumor-associated macrophages. Taken together, we demonstrated that THP-1-derived macrophages polarized to a phenotype of M2-like characteristics when subjected to chronic iron overload.

中文翻译:

慢性铁过载下THP-1单核细胞衍生巨噬细胞的M2样极化。

巨噬细胞的特征在于表型和功能异质性。在不同的微环境中,巨噬细胞可极化为两种类型:经典活化的巨噬细胞(M1)或可替代的活化的巨噬细胞(M2)。M1巨噬细胞是众所周知的抑菌巨噬细胞,相反,M2巨噬细胞可能在肿瘤生长和组织重塑中起重要作用。据报道,M1巨噬细胞具有较高的细胞内铁储存,而M2巨噬细胞含有较低的细胞内铁。众所周知,铁稳态的紊乱与免疫功能的改变有关。因此,重要的是研究慢性铁超负荷是否能够使巨噬细胞极化。将人单核细胞白血病THP-1细胞保存在含有100μM七水合硫酸亚铁(FeSO4)(I-THP-1)的培养基中,并通过佛波醇12-肉豆蔻酸酯诱导分化为THP-1衍生的巨噬细胞(I-TDMs)。 13-乙酸盐(PMA)。我们的特征是I-TDMs不仅增强了CD163和CD206的表面表达,而且还增加了精氨酸酶和iNOS蛋白的表达。I-TDMs增强pSTAT6表达,降低pSTAT1和NF-κB表达。此外,通过进行人寡核苷酸DNA微阵列分析,I-TDM的基因表达谱与M2巨噬细胞相当。最后,功能分析表明I-TDM分泌更高水平的IL-10,但不分泌M1细胞因子。另外,I-TDMs的条件培养基具有增强的A375黑色素瘤细胞迁移和侵袭能力,这与肿瘤相关巨噬细胞的特征相似。两者合计,我们证明了THP-1衍生的巨噬细胞在遭受慢性铁超负荷时会极化成M2类特征的表型。
更新日期:2020-02-01
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