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Receptor-mediated tobacco toxicity: alterations of the NF-kappaB expression and activity downstream of alpha7 nicotinic receptor in oral keratinocytes.

Authors
  • Arredondo, Juan
  • Chernyavsky, Alexander I
  • Jolkovsky, David L
  • Pinkerton, Kent E
  • Grando, Sergei A
Type
Published Article
Journal
Life Sciences
Publisher
Elsevier
Publication Date
May 30, 2007
Volume
80
Issue
24-25
Pages
2191–2194
Identifiers
PMID: 17291542
Source
Medline
License
Unknown

Abstract

To gain a mechanistic insight into nicotinic receptor-dependent morbidity of tobacco products in the oral cavity, we studied effects of exposures of normal human oral keratinocytes (KCs) for 24 h to environmental tobacco smoke (ETS) vs. equivalent concentration of pure nicotine. The exposed KCs showed a multifold increase of nuclear factor-kappaB (NF-kappaB) at the mRNA and protein levels, which could be significantly (p<0.05) diminished by alpha-bungarotoxin or transfection with anti-alpha7 small interfering RNA. An increased protein-binding activity of NF-kappaB also could be prevented by blocking alpha7 signaling. The use of pathway inhibitors demonstrated that the Ras/Raf-1/MEK1/ERK steps mediated alpha7-dependent upregulation of NF-kappaB. Thus, exposure of KCs to tobacco may lead to the pathobiologic effects via an intracellular signaling pathway downstream of alpha7 that proceeds through the Ras/Raf-1/MEK1/ERK steps leading to upregulated expression and transactivation of NF-kappaB.

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