Environmental tobacco smoke suppresses nuclear factor-kappaB signaling to increase apoptosis in infant monkey lungs

Am J Respir Crit Care Med. 2006 Aug 15;174(4):428-36. doi: 10.1164/rccm.200503-509OC. Epub 2006 May 18.


Rationale: Exposure to environmental tobacco smoke in early life has adverse effects on lung development. Apoptosis plays an essential role in development; however, the molecular mechanisms of pulmonary apoptosis induced by environmental tobacco smoke is unknown.

Objectives: To investigate the mechanistic role of nuclear factor (NF)-kappaB, a critical cell survival pathway, in the developing lungs exposed to environmental tobacco smoke.

Methods: Timed-pregnant rhesus monkeys and their offspring were exposed to filtered air or to aged and diluted sidestream cigarette smoke as a surrogate to environmental tobacco smoke (a total suspended particulate concentration of 0.99 mg/m(3) for 6 h/d, 5 d/wk) from 45-50 d gestational age to 72-77 d postnatal age (n = 4/group).

Measurements and main results: NF-kappaB-DNA binding activity, regulated anti-apoptotic genes, and apoptosis were measured in lung tissues. Exposure to environmental tobacco smoke significantly suppressed NF-kappaB activation pathway and activity. Environmental tobacco smoke further down-regulated NF-kappaB-dependent anti-apoptotic genes and induced activation of caspases, cleavage of cellular death substrates (poly(ADP)-ribose polymerase and caspase-activated DNase) and an increase in the rate of apoptosis in the lung parenchyma. No significant alterations were observed for activator protein 1, p53 or Akt activity.

Conclusions: Our results indicate that exposure to low levels of environmental tobacco smoke during a critical window of maturation in the neonatal nonhuman primate may compromise lung development with potential implications for future lung growth and function. These findings support our hypothesis that NF-kappaB plays a key role in the regulation of the apoptotic process.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / physiology*
  • Electrophoretic Mobility Shift Assay
  • Female
  • Lung / growth & development
  • Lung / physiology*
  • Macaca mulatta
  • Models, Theoretical
  • NF-kappa B / physiology*
  • Pregnancy
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Smoke / adverse effects*
  • Tobacco Smoke Pollution*


  • NF-kappa B
  • Smoke
  • Tobacco Smoke Pollution