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MT-2 细胞系中细胞表型的多样性会影响 U937 细胞的生长和细胞因子的产生。

Diversity of cell phenotypes among MT-2 cell lines affects the growth of U937 cells and cytokine production.

机构信息

Department of Rheumatology, Infectious Diseases and Laboratory Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.

Department of Life Medical, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki, 882-8508, Japan.

出版信息

Hum Cell. 2019 Apr;32(2):185-192. doi: 10.1007/s13577-018-00231-3. Epub 2018 Dec 17.

Abstract

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)-α, TNF-β, and interferon (IFN)-γ 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-β and its synergic effects with IFN-γ 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.

摘要

我们之前曾报道过人 T 细胞白血病病毒 1(HTLV-1)前病毒在不同 MT-2 细胞系中的结构和整合位点多样性。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。本研究调查了两种不同的 MT-2 细胞系(MT-2J 和 MT-2B)对 promonocytic 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 blot 分析。来自 MT-2B 而非 MT-2J 的细胞培养上清液对 U937 细胞生长具有明显的抑制作用。MT-2B 细胞培养上清液和细胞中 TNF-α、TNF-β 和 IFN-γ 的蛋白水平和 mRNA 水平均较高。使用重组细胞因子的分析表明,MT-2B 的抑制作用至少部分归因于培养上清液中 TNF-β 水平较高及其与 IFN-γ 的协同作用。MT-2B 细胞中 HTLV-1 Tax 和 HBZ 的蛋白水平高于 MT-2J 细胞。这些分子已被报道会影响 HTLV-1 感染细胞的细胞因子产生;因此,这些分子的差异可能导致了 MT-2J 和 MT-2B 细胞之间细胞因子产生的差异。此外,由于 MT-2 细胞表现出整合的 HTLV-1 前病毒和细胞表型的巨大变化,因此在评估和解释 MT-2 细胞的实验数据时需要谨慎。

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