Diversity of cell phenotypes among MT-2 cell lines affects the growth of U937 cells and cytokine production
Diversity of cell phenotypes among MT-2 cell lines affects the growth of U937 cells and cytokine production
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DOI：
10.1007/s13577-018-00231-3
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发表时间：
2019-04-01
期刊：
影响因子：
4.3
通讯作者：
Okayama, Akihiko
中科院分区：
文献类型：
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作者：
Nomura, Hajime;Umekita, Kunihiko;Okayama, Akihiko
我们先前报道了不同MT-2细胞系中人T细胞白血病病毒1型（HTLV-1）前病毒的结构和整合位点的多样性。这就提出了一个问题，即MT-2细胞系之间的细胞表型是否也存在差异。研究了两种不同的MT-2细胞系（MT-2 J和MT-2B）对前单核细胞白血病细胞系U937生长的影响。还研究了细胞因子的蛋白水平和mRNA表达。此外，还进行了HTLV-1调节蛋白Tax和HBZ的Western印迹分析。MT-2B细胞培养上清对U937细胞生长有明显的抑制作用，而MT-2 J细胞培养上清对U937细胞生长无明显抑制作用。MT-2B在培养上清液的蛋白水平和细胞的mRNA水平上显示出高的肿瘤坏死因子（TNF）-、TNF-和干扰素（IFN）-。使用重组细胞因子的分析表明，MT-2B的抑制作用是由于，至少部分是由于高水平的TNF-α及其与IFN-α的协同作用，在培养上清液中。MT-2B细胞中HTLV-1 Tax和HBZ蛋白水平高于MT-2 J细胞。据报道，这些分子影响HTLV-1感染细胞的细胞因子产生;因此，这些分子的差异可能是MT-2 J和MT-2B细胞之间细胞因子产生差异的原因。此外，由于MT-2细胞显示出整合的HTLV-1前病毒以及细胞表型的较大变化，因此在评估和解释MT-2细胞的实验数据时应谨慎。
We previously reported the diversity of structure and integration sites of human T-cell leukemia virus type 1 (HTLV-1) provirus among different MT-2 cell lines. This raised the question as to whether cell phenotypes also differed among MT-2 cell lines. The influence of two different MT-2 cell lines (MT-2J and MT-2B) on the growth of the promonocytic leukemia cell line, U937, was investigated. Protein levels and mRNA expression of cytokines were also investigated. In addition, Western blot analysis of HTLV-1 regulatory proteins, Tax and HBZ, was also performed. Culture supernatant from MT-2B, but not MT-2J, cells showed marked suppressive effects on U937 cell growth. MT-2B showed high tumor necrosis factor (TNF)-, TNF-, and interferon (IFN)- both in protein levels of the culture supernatant and mRNA levels of the cells. Analysis using recombinant cytokines indicated that the suppressive effects of MT-2B were due, at least in part, to high levels of TNF- and its synergic effects with IFN- in the culture supernatant. Protein levels of HTLV-1 Tax and HBZ were higher in MT-2B than those in MT-2J cells. These molecules have been reported to affect the cytokine production of HTLV-1 infected cells; therefore, the difference in these molecules may have accounted for the differences in cytokine production between MT-2J and MT-2B cells. Furthermore, because MT-2 cells showed a large variation of integrated HTLV-1 proviruses as well as cell phenotypes, it is important to exercise caution in the assessment and interpretation of experimental data from MT-2 cells.