Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Nicotine Suppresses TNF-${\alpha}$ Expression in Human Fetal Astrocyte through the Modulation of Nuclear Factor-${\kappa}B$ Activation

  • Son, Il-Hong (Department of Neurology, Sanbon Medical Center, Wonkwang University) ;
  • Park, Yong-Hoon (Inam Neuroscience Research Center, Sanbon Medical Center, Wonkwang University) ;
  • Yang, Hyun-Duk (Department of Neurology, Sanbon Medical Center, Wonkwang University) ;
  • Lee, Sung-Ik (Department of Neurology, Sanbon Medical Center, Wonkwang University) ;
  • Han, Sun-Jung (Department of Neurology, Sanbon Medical Center, Wonkwang University) ;
  • Lee, Jai-Kyoo (Department of Emergency Medicine, Sanbon Medical Center, Wonkwang University) ;
  • Ha, Dae-Ho (Department of Orthopedics Sanbon Medical Center, Wonkwang University) ;
  • Kang, Hyung-Won (Department of Oriental Neuropsychiatry, Sanbon Oriental Medical Center, Wonkwang University) ;
  • Park, Joo-Young (Department of Microbiology, Wonju College of Medicine, Yonsei University) ;
  • Lee, Sung-Soo (Department of Neurology, Wonju College of Medicine, Yonsei University)
  • Published : 2008.06.30
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Abstract

Parkinson's disease (PD) progresses severely by a gradual loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological studies showed that the incidences of PD were reduced by smoking of which the major component, nicotine might be neuroprotective. But the function of nicotine, which might suppress the incidences of PD, is still unknown. Fortunately, recently it was reported that a glial reaction and inflammatory processes might participate in a selective loss of dopaminergic neurons in the SN. The levels of tumour necrosis factor (TNF)-${\alpha}$ synthesised by astrocytes and microglia are elevated in striatum and cerebrospinal fluid (CSF) in PD. TNF-${\alpha}$ kills the cultured dopaminergic neurons through the apoptosis mechanism. TNF-${\alpha}$ release from glial cells may mediate progression of nigral degeneration in PD. Nicotine pretreatment considerably decreases microglial activation with significant reduction of TNF-${\alpha}$ mRNA expression and TNF-${\alpha}$ release induced by lipopholysaccharide (LPS) stimulation. Thus, this study was intended to explore the role of nicotine pretreatment to inhibit the expressions of TNF-${\alpha}$ mRNA in human fetal astrocytes (HFA) stimulated with IL-$1{\beta}$. The results are as follows: HFA were pretreated with 0.1, 1, and $10{\mu}g/mL$ of nicotine and then stimulated with IL-$1{\beta}$ (100 pg/mL) for 2h. The inhibitory effect of nicotine on expressions of TNF-${\alpha}$ mRNA in HFA with pretreated $0.1{\mu}g/mL$ of nicotine was first noted at 8hr, and the inhibitory effect was maximal at 12 h. The inhibitory effect at $1{\mu}g/mL$ of nicotine was inhibited maximal at 24 h. Cytotoxic effects of nicotine were noted above $10{\mu}g/mL$ of nicotine. Moreover, Nicotine at 0.1, 1 and $10{\mu}g/mL$concentrations significantly inhibited IL-$1{\beta}$-induced TF-${\kappa}B$ activation. Collectively, these results indicate that in activated HFA, nicotine may inhibit the expression of TNF-${\alpha}$ mRNA through the pathway which suppresses the NF-${\kappa}B$ activation. This study suggests that nicotine might be neuroprotective to dopaminergic neurons in the SN and reduce the incidences of PD.

Keywords

References

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