The interaction of butyrate with TNF-α during differentiation and apoptosis of colon epithelial cells: Role of NF-κB activation

The interaction of butyrate with TNF-α during differentiation and apoptosis of colon epithelial cells: Role of NF-κB activation
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DOI:
10.1016/j.cyto.2008.06.003
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发表时间:
2008-10-01
期刊:
影响因子:
3.8
通讯作者:
Kozubik, A.
Kozubik, A.
中科院分区:
医学3区
文献类型:
--
作者:
Hyzd'alova, M.;Hofmanova, J.;Kozubik, A.

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我们在体外证明,TNF-α 可抑制腺癌 HT-29 和胎儿 FHC 人结肠细胞中丁酸盐 (NaBt) 诱导的分化并增强细胞死亡。由于TNF-α是NF-κB途径的典型激活剂,我们研究了TNF-α和NaBt联合治疗期间NF-κB激活在细胞分化和死亡中的作用。 TNF-α 在 HT-29 和 FHC 细胞系中诱导 NF-κ B 快速激活,并且 NaBt 在这两种细胞系中对这种效应的调节不同。在 HT-29 细胞中,NaBt 处理 4 小时后可增强 TNF-α 诱导的 NF-κ B 活性。然而,在 FHC 细胞中并未观察到 NF-κ B 活性的这种初始增强。在 TNF-α 和 NaBt 共同治疗的额外时间内,NaBt 降低了两种细胞类型中 TNF-α 介导的 NF-κ B 活性。我们还检测到 HT-29 和 FHC 细胞在用 NF-κ B 抑制剂小白菊内酯预处理后有不同的反应。我们的结果表明,NaBt 介导的结肠上皮细胞分化和凋亡可以通过 TNF-α 进行调节。此外,我们发现非癌症和癌症来源的细胞之间 NaBt 和 TNF-α 共同治疗作用的机制存在显着差异,这表明 NF-κ B 通路可能更有效地参与癌细胞中的这些过程。 (C) 2008 Elsevier Ltd. 保留所有权利。
We demonstrated that TNF-alpha suppressed differentiation and potentiated cell death induced by butyrate (NaBt) in both adenocarcinoma HT-29 and fetal FHC human colon cells in vitro. Since TNF-alpha is a typical activator of NF-kappa B pathway, we studied the role of NF-kappa B activation in cell differentiation and death during the TNF-alpha and NaBt co-treatment. TNF-alpha induced rapid NF-kappa B activation in both HT-29 and FHC cell lines and this effect was differently modulated by NaBt in these two cell lines. In HT-29 cells, NaBt potentiated NF-kappa B activity induced by TNF-alpha after 4 h treatment. However, this initial potentiation of NF-kappa B activity was not observed in FHC cells. During additional time of TNF-alpha and NaBt co-treatment, NaBt decreased the TNF-alpha-mediated NF-kappa B activity in both cell types. We also detected a different response of HT-29 and FHC cells after the pre-treatment with the NF-kappa B inhibitor parthenolide. Our results indicated that NaBt-mediated differentiation and apoptosis of colon epithelial cells can be modulated by TNF-alpha. Furthermore, we found significant differences in the mechanism of the NaBt and TNF-alpha co-treatment effects between cells of non-cancer and cancer origin, suggesting that the NF-kappa B pathway may be more effectively involved in these processes in cancer cells. (C) 2008 Elsevier Ltd. All rights reserved.