Inhibition of nuclear factor-[kappa]B activation is essential for membrane-associated TNF-[alpha]-induced apoptosis in HL-60 cells

• Published in: Immunology and cell biology 2006-08, Vol.84 (4), p.366
• Main Authors: Shi, Wenfang, Li, Lingyun, Shi, Xu, Zheng, Fang, Zeng, Jingyang, Jiang, Xiaodan, Gong, Feili, Zhou, Muxiang, Li, Zhuoya
• Format: Article
• Language: English
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1111/j.1440-1711.2006.01436.x

SummaryThe killing of tumour cells that are resistant to soluble TNF-α (sTNF-α) by the membrane-bound form of TNF-α (mTNF-α) suggests that different intracellular signalling pathways are involved. We found that mTNF-α induced apoptosis in HL-60 cells and failed to cause degradation of inhibitor of kappa B alpha (IκB-α) and translocation and activation of nuclear factor kappa B (NF-κB), whereas sTNF-α failed to induce apoptosis, but lowered cytoplasmic inhibitor of kappa B alpha, induced translocation of NF-κB to the nucleus and experimentally increased activity of the regulated luciferase. Furthermore, mTNF-α upregulated the expression of TNF receptor associated factor (TRAF) 1 and failed to induce TRAF1 and TRAF2 membrane translocation, but led to cytoplasmic colocalization. In contrast, sTNF-α stimulated the expression of TRAF1 and TRAF2, recruiting both molecules onto the cell membrane poststimulation. These results suggest that the increased susceptibility of HL-60 cells to mTNF-α may be due to the failure of TRAF2 membrane translocation caused by the upregulation of TRAF1 expression and formation of a TRAF1/TRAF2 complex in the cytoplasm, thereby inhibiting NF-κB activation and inducing apoptosis.