TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: Transcriptional activation of I kappa B alpha
TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: Transcriptional activation of I kappa B alpha
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DOI：
10.1016/s1074-7613(00)80307-6
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发表时间：
1996-07-01
期刊：
影响因子：
32.4
通讯作者：
Sonenshein, GE
中科院分区：
文献类型：
--
作者：
Arsura, M;Wu, M;Sonenshein, GE
B 细胞淋巴瘤的 TGF beta 1 治疗会降低 c-myc 基因表达并诱导细胞凋亡。由于我们已经证明 NF-kappa B/Rel 因子在 c-myc 转录控制中发挥关键作用，因此我们探讨了 TGF beta 1 对 WEHI 231 未成熟 B 细胞的影响。 TGF beta 1 治疗后 NF-κ B/Rel 活性降低。在 WEHI 231 和 CH33 细胞中，我们观察到由于转录诱导，I kappa B α（一种特定的 NF-kappa B/Rel 抑制剂）增加。表面 CD40 或异位 c-Rel 的参与导致 NF-kappa B/Rel 和 c-Myc 表达的维持，并保护 WEHI 231 细胞免受 TGF beta 1 介导的细胞凋亡。异位 c-Myc 表达超过了 TGF beta 1 诱导的细胞凋亡。因此，下调 NF-kappa B/Rel 会降低 c-Myc 表达，从而导致这些克隆缺失的未成熟 B 细胞模型发生细胞凋亡。 NF-κ B/Rel 活性的抑制代表了一种新的 TGF beta 信号传导机制。
TGF beta 1 treatment of B cell lymphomas decreases c-myc gene expression and induces apoptosis. Since we have demonstrated NF-kappa B/Rel factors play a key role in transcriptional control of c-myc, we explored the effects of TGF beta 1 on WEHI 231 immature B cells. A reduction in NF-kappa B/Rel activity followed TGF beta 1 treatment. In WEHI 231 and CH33 cells, we observed an increase in I kappa B alpha, a specific NF-kappa B/Rel inhibitor, due to transcriptional induction. Engagement of surface CD40 or ectopic c-Rel led to maintenance of NF-kappa B/ Rel and c-Myc expression and protection of WEHI 231 cells from TGF beta 1-mediated apoptosis. Ectopic c-Myc expression overrode apoptosis induced by TGF beta 1. Thus, downmodulation of NF-kappa B/Rel reduces c-Myc expression, which leads to apoptosis in these immature B cell models of clonal deletion. The inhibition of NF-kappa B/Rel activity represents a novel TGF beta signaling mechanism.