Receptor-mediated tobacco toxicity: Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes

Juan Arredondo, Alexander I. Chernyavsky, David L. Jolkovsky, Kent E Pinkerton, Sergei A. Grando

Research output: Contribution to journalArticle

38 Citations (Scopus)

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-κB (NF-κB) at the mRNA and protein levels, which could be significantly (p < 0.05) diminished by α-bungarotoxin or transfection with anti-α7 small interfering RNA. An increased protein-binding activity of NF-κB also could be prevented by blocking α7 signaling. The use of pathway inhibitors demonstrated that the Ras/Raf-1/MEK1/ERK steps mediated α7-dependent upregulation of NF-κB. Thus, exposure of KCs to tobacco may lead to the pathobiologic effects via an intracellular signaling pathway downstream of α7 that proceeds through the Ras/Raf-1/MEK1/ERK steps leading to upregulated expression and transactivation of NF-κB.

Original languageEnglish (US)
Pages (from-to)2191-2194
Number of pages4
JournalLife Sciences
Volume80
Issue number24-25
DOIs
StatePublished - May 30 2007

Fingerprint

Tobacco
Nicotinic Receptors
Keratinocytes
Toxicity
Bungarotoxins
Nicotine
Protein Binding
Smoke
Tobacco Products
Small Interfering RNA
Transcriptional Activation
Transfection
Mouth
Up-Regulation
Morbidity
Messenger RNA
Proteins

Keywords

  • ERK
  • Gene expression
  • MEK
  • NF-κB
  • Nicotinic acetylcholine receptors
  • Raf
  • Ras

ASJC Scopus subject areas

  • Pharmacology

Cite this

Receptor-mediated tobacco toxicity : Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes. / Arredondo, Juan; Chernyavsky, Alexander I.; Jolkovsky, David L.; Pinkerton, Kent E; Grando, Sergei A.

In: Life Sciences, Vol. 80, No. 24-25, 30.05.2007, p. 2191-2194.

Research output: Contribution to journalArticle

Arredondo, Juan ; Chernyavsky, Alexander I. ; Jolkovsky, David L. ; Pinkerton, Kent E ; Grando, Sergei A. / Receptor-mediated tobacco toxicity : Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes. In: Life Sciences. 2007 ; Vol. 80, No. 24-25. pp. 2191-2194.
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