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 language | English (US) |
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Pages (from-to) | 2191-2194 |
Number of pages | 4 |
Journal | Life Sciences |
Volume | 80 |
Issue number | 24-25 |
DOIs | |
State | Published - May 30 2007 |
Keywords
- ERK
- Gene expression
- MEK
- NF-κB
- Nicotinic acetylcholine receptors
- Raf
- Ras
ASJC Scopus subject areas
- Pharmacology