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α干扰素和γ干扰素对人骨髓瘤细胞系U-266及α干扰素抗性U-266亚系中IgE和β2-微球蛋白增殖与产生的影响

The effect of alpha and gamma-interferon on proliferation and production of IgE and beta 2-microglobulin in the human myeloma cell line U-266 and in an alpha-interferon resistant U-266 subline.

作者信息

Brenning G, Jernberg H, Gidlund M, Sjöberg O, Nilsson K

出版信息

Scand J Haematol. 1986 Oct;37(4):280-8. doi: 10.1111/j.1600-0609.1986.tb02313.x.

DOI:10.1111/j.1600-0609.1986.tb02313.x
PMID:3097807
Abstract

An IFN-resistant subline (U-266r alpha) was established from the IFN-alpha-sensitive myeloma cell line U-266 by subculturing U-266 cells with increasing doses of INF-alpha. The U-266r alpha secreted IgE at a higher rate than the U-266 (7.2 X 10(-13) g/c/8 h as compared to 3.3 X 10(-13) g/c/8 h). The 2 cell lines were found to be equally high producers of beta 2m (9.2 and 9.6 X 10(-13) g/c/8 h). The U-266 produced 2.9 times less IgE and 5 times more beta 2m compared to the initial production rates at establishment. INF-alpha and recombinant IFN-alpha 2 (rIFN-alpha 2) inhibited proliferation and concomitantly decreased the rate of IgE and beta 2m secretion in U-266 but not in U-266 IFNr alpha, which in contrast was slightly stimulated by IFN-alpha with respect to growth, IgE and beta 2m secretion. In addition, IFN-alpha at a concentration of 100 U/ml was shown to decrease the IgE and beta 2m production without exerting more than minimal cytotoxicity on U-266 cells. No antiproliferative effect was found for IFN-gamma or recombinant IFN-gamma (rIFN-gamma) on either of the 2 cell lines. IFN-gamma and rIFN-gamma were, however, found to stimulate the production of beta 2m. Our results show that the U-266 and the derived IFN-alpha-resistant subline can be used as models for studying some of the biological effects of IFN-alpha and -gamma in vitro. The clinical implications of these in vitro results, in particular the usefulness of serum determinations of immunoglobulin and beta 2m concentrations for monitoring the tumor cell mass, are discussed.

摘要

通过用递增剂量的干扰素-α(IFN-α)传代培养U-266细胞,从对IFN-α敏感的骨髓瘤细胞系U-266建立了一个IFN抗性亚系(U-266rα)。U-266rα分泌IgE的速率高于U-266(分别为7.2×10⁻¹³克/细胞/8小时和3.3×10⁻¹³克/细胞/8小时)。发现这两种细胞系都是β2微球蛋白(β2m)的高产细胞(分别为9.2和9.6×10⁻¹³克/细胞/8小时)。与建立时的初始产生率相比,U-266产生的IgE减少了2.9倍,β2m增加了5倍。IFN-α和重组IFN-α2(rIFN-α2)抑制U-266细胞的增殖,并同时降低IgE和β2m的分泌速率,但对U-266 IFNrα无此作用,相反,IFN-α对U-266 IFNrα的生长、IgE和β2m分泌有轻微刺激作用。此外,浓度为100 U/ml的IFN-α可降低IgE和β2m的产生,且对U-266细胞的细胞毒性不超过最小限度。未发现IFN-γ或重组IFN-γ(rIFN-γ)对这两种细胞系有抗增殖作用。然而,发现IFN-γ和rIFN-γ可刺激β2m的产生。我们的结果表明,U-266及其衍生的IFN-α抗性亚系可作为体外研究IFN-α和-γ某些生物学效应的模型。讨论了这些体外结果的临床意义,特别是血清免疫球蛋白和β2m浓度测定对监测肿瘤细胞量的有用性。

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引用本文的文献

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Med Oncol. 2001;18(1):3-14. doi: 10.1385/mo:18:1:3.
2
Differential human multiple myeloma cell line responsiveness to interferon-alpha. Analysis of transcription factor activation and interleukin 6 receptor expression.人多发性骨髓瘤细胞系对α干扰素的不同反应性。转录因子激活及白细胞介素6受体表达分析。
J Clin Invest. 1997 Feb 1;99(3):447-56. doi: 10.1172/JCI119179.
3
Disruption by interferon-alpha of an autocrine interleukin-6 growth loop in IL-6-dependent U266 myeloma cells by homologous and heterologous down-regulation of the IL-6 receptor alpha- and beta-chains.
通过白细胞介素-6受体α链和β链的同源和异源下调,干扰素-α破坏白细胞介素-6依赖性U266骨髓瘤细胞中的自分泌白细胞介素-6生长环。
J Clin Invest. 1994 Dec;94(6):2317-25. doi: 10.1172/JCI117596.
4
Interferon-alpha down-regulates the interleukin-6 receptor in a human multiple myeloma cell line, U266.α干扰素可下调人多发性骨髓瘤细胞系U266中的白细胞介素-6受体。
Biochem J. 1995 Jul 1;309 ( Pt 1)(Pt 1):175-80. doi: 10.1042/bj3090175.