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

Cai Yun Zhong, Mei Zhou Ya, Jesse P. Joad, Kent E Pinkerton

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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)-κB, 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/m3 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-κB-DNA binding activity, regulated anti-apoptotic genes, and apoptosis were measured in lung tissues. Exposure to environmental tobacco smoke significantly suppressed NF-κB activation pathway and activity. Environmental tobacco smoke further down-regulated NF-κB-dependent antiapoptotic 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-κB plays a key role in the regulation of the apoptotic process.

Original languageEnglish (US)
Pages (from-to)428-436
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number4
StatePublished - Aug 15 2006


  • Apoptosis
  • Environmental tobacco smoke
  • Infant monkeys
  • Lung development
  • NF-κB

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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