NF-κB signalling and cell fate decisions in response to a short pulse of tumour necrosis factor

Sci Rep. 2016 Dec 22;6:39519. doi: 10.1038/srep39519.

Abstract

In tissues and tumours, cell behaviours are regulated by multiple time-varying signals. While in the laboratory cells are often exposed to a stimulus for the duration of the experiment, in vivo exposures may be much shorter. In this study, we monitored NF-κB and caspase signalling in human cancer cells treated with a short pulse of Tumour Necrosis Factor (TNF). TNF is an inflammatory cytokine that can induce both the pro-survival NF-κB-driven gene transcription pathway and the pro-apoptotic caspase pathway. We find that a few seconds of exposure to TNF is sufficient to activate the NF-κB pathway in HeLa cells and induce apoptotic cell death in both HeLa and Kym-1 cells. Strikingly, a 1-min pulse of TNF can be more effective at killing than a 1-hour pulse, indicating that in addition to TNF concentration, duration of exposure also coordinates cell fate decisions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Apoptosis*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Lineage*
  • Cytokines / metabolism
  • HeLa Cells
  • Humans
  • Inflammation
  • Microfluidics
  • NF-kappa B p50 Subunit / metabolism*
  • Signal Transduction
  • Time Factors
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Cytokines
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • RELA protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Caspases