Arsura M, Wu M, Sonenshein G E
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Immunity. 1996 Jul;5(1):31-40. doi: 10.1016/s1074-7613(00)80307-6.
TGF beta 1 treatment of B cell lymphomas decreases c-myc gene expression and induces apoptosis. Since we have demonstrated NF-kappa/Rel factors play a key role in transcriptional control of c-myc, we explored the effects of TGF beta1 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.
转化生长因子β1（TGFβ1）治疗B细胞淋巴瘤可降低c-myc基因表达并诱导细胞凋亡。由于我们已证明核因子κB/Rel因子在c-myc的转录调控中起关键作用，因此我们探究了TGFβ1对WEHI 231未成熟B细胞的影响。TGFβ1处理后核因子κB/Rel活性降低。在WEHI 231和CH33细胞中，我们观察到由于转录诱导，特异性核因子κB/Rel抑制剂IκBα增加。表面CD40的激活或异位表达的c-Rel可维持核因子κB/Rel和c-Myc表达，并保护WEHI 231细胞免受TGFβ1介导的细胞凋亡。异位表达的c-Myc可克服TGFβ1诱导的细胞凋亡。因此，核因子κB/Rel的下调会降低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。抑制核因子κB/Rel活性代表了一种新的TGFβ信号传导机制。
