1. Academic Validation
  2. Theophylline inhibits NF-kappa B activation and I kappa B alpha degradation in human pulmonary epithelial cells

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.
T Ichiyama 1 S Hasegawa T Matsubara T Hayashi S Furukawa
Affiliations

Affiliation

  • 1 Department of Pediatrics, Yamaguchi University School of Medicine, Ube, Japan. ichiyama@po.cc.yamaguchi-u.ac.jp
Abstract

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.

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