Transforming growth factor-beta 1 inhibits activation of macrophage cell line RAW 264.7 for cell killing.

Transforming growth factor-beta 1 inhibits activation of macrophage cell line RAW 264.7 for cell killing.
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转化生长因子-β 1 抑制巨噬细胞系 RAW 264.7 的活化以杀死细胞。

DOI:
10.1111/j.1365-2249.1990.tb05461.x
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发表时间:
1990
影响因子:
4.6
通讯作者:
Paulnock,D
Paulnock,D
中科院分区:
医学3区
文献类型:
--
作者:
Haak-Frendscho,M;Wynn,TA;Czuprynski,CJ;Paulnock,D

文献摘要

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转化生长因子β-1(TGF-β)是一种多能免疫调节肽,对多种细胞类型具有作用。在这里,我们报告了人TGF-β抑制巨噬细胞系RAW 264.7的活化以杀死L1210肿瘤细胞系。RAW 264.7细胞与正常巨噬细胞一样,需要与引发和触发刺激物顺序相互作用以完全激活溶细胞活性。TGF-β在引发和触发阶段均以剂量依赖性方式抑制这种细胞毒性。当与引发信号(重组干扰素-γ(IFN-γ))或触发信号(细菌脂多糖(LPS))一起添加时,添加低至lng/ml的TGF-β完全消除杀肿瘤活性。与TGF-β孵育还抑制了在活化的RAW 264.7细胞中正常观察到的形态学变化。然而. TGF-β不能抑制RAW 264.7细胞对靶细胞系WEHI 164的细胞毒活性,WEHI 164对肿瘤坏死因子敏感。与对细胞毒活性的影响相反,活化RAW 264.7细胞的细胞抑制活性在高达5 ng/ml的剂量下不受TGF-β抑制。此外,用TGF-β预处理LI 210靶细胞使其对RAW 264.7细胞的细胞生长抑制和细胞毒性作用均不敏感。这些数据表明,TGF-β可能是调节巨噬细胞杀肿瘤活性的重要介质。
Transforming growth factor β-1 (TGF-β) is a multi-potent immunoregulatory peptide that has effects on numerous cell types. Here we report that human TGF-β inhibits the activation of the macrophagc cell line RAW 264.7 for killing of the L1210 tumour cell line. RAW 264.7 cells, like normal macrophages, require sequential interaction with priming and triggering stimuli for full activation of cytolytic activity. TGF-β inhibits this cytotoxicity in a dose-dependent manner at both the priming and the triggering stage. Addition of as little as 1 ng/ml TGF-β when added with either the priming signal, recombinant interferon-gamma (IFN-γ), or the triggering signal, bacterial lipopolysaccharide (LPS), completely abrogated tumouricidal activity. Incubation with TGF-β also inhibited the morphological changes normally observed in activated RAW 264.7 cells. However. TGF-β was unable to inhibit the cytotoxic activity of RAW 264.7 cells against the target cell line WEHI 164, which is sensitive to tumour necrosis factor. In contrast to the effects on cytotoxic activity, the cytostatic activity of activated RAW 264.7 cells was not inhibited by TGF-β at doses of up to 5 ng/ml. In addition, pretreatment of the LI210 target cells with TGF-β made them refractory to both the cytostatic and cytotoxic effects of RAW 264.7 cells. These data suggest that TGF-β may be an important mediator in the regulation of macrophage tumouricidal activity.