Theophylline inhibits NF-kappa B activation and I kappa B alpha degradation in human pulmonary epithelial cells

Naunyn Schmiedebergs Arch Pharmacol. 2001 Dec;364(6):558-61. doi: 10.1007/s00210-001-0494-x.


Previous studies demonstrated that theophylline modulates NF-kappaB activation in mast cells and pulmonary epithelial cells. We examined whether or not this modulation of NF-kappaB activation by theophylline is due to inhibition of the degradation of the IKBalpha protein, which suppresses NF-kappaB activation. TNF-alpha-induced NF-kappaB activation in a human pulmonary epithelial cell line (A549) was evaluated by Western blotting and a chloramphenicol acetyltransferase (CAT) assay. Expression of the IkappaBalpha protein was evaluated by Western blotting. Western blotting of nuclear extracts of A549 cells demonstrated that theophylline suppresses NF-kappaB-p65 nuclear translocation. The CAT assay indicated that NF-kappaB-dependent reporter gene expression is inhibited in A549 cells pretreated with theophylline. Western blotting of cytoplasmic extracts of A549 cells revealed that this inhibition was linked to theophylline-induced protection of expression of the IkappaBalpha protein. Moreover, theophylline inhibited interleukin-6 production induced by TNF-alpha in A549 cells. These findings are consistent with the idea that theophylline suppresses the production of proinflammatory cytokines via inhibition of NF-kappaB activation through protection of the IkappaBalpha protein.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Bronchodilator Agents / pharmacology
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • I-kappa B Proteins*
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism
  • Lung / cytology
  • Lung / drug effects*
  • Lung / metabolism*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Phosphodiesterase Inhibitors / pharmacology
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / metabolism*
  • Theophylline / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Bronchodilator Agents
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Interleukin-6
  • NF-kappa B
  • NFKBIA protein, human
  • Phosphodiesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Theophylline