Inhibition of nuclear factor-κB activation is essential for membrane-associated TNF-α-induced apoptosis in HL-60 cells

• Published in: Immunology and cell biology 2006-08, Vol.84 (4), p.366-373
• Main Authors: Shi, Wenfang, Li, Lingyun, Shi, Xu, Zheng, Fang, Zeng, Jingyang, Jiang, Xiaodan, Gong, Feili, Zhou, Muxiang, Li, Zhuoya
• Format: Article
• Language: English
• Subjects: apoptosis; membrane‐bound form of TNF‐α (mTNF‐α); nuclear factor kappa B (NF‐κB); soluble TNF‐α (sTNF‐α); TNF receptor associated factor 1 (TRAF1); TRAF2
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1111/j.1440-1711.2006.01436.x

The 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.