Inhibition of iNOS Expression Via Ursodeoxycholic Acid in Murine Microglial Cell, BV-2 Cell Line

생쥐 소교세포(BV-2)에서 우르소데옥시콜린산에 의한 iNOS 발현억제

  • Joo, Seong-Soo (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Won, Tae-Joon (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Hwang, Kwang-Woo (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Lee, Do-Ik (Department of Immunology, College of Pharmacy, Chung-Ang University)
  • 주성수 (중앙대학교 약학대학 면역학교실) ;
  • 원태준 (중앙대학교 약학대학 면역학교실) ;
  • 황광우 (중앙대학교 약학대학 면역학교실) ;
  • 이도익 (중앙대학교 약학대학 면역학교실)
  • Published : 2005.03.31

Abstract

Background: Inflammation in the brain has known to be associated with the development of a various neurological diseases. The hallmark of neuro-inflammation is the activation of microglia, brain macrophage. Pro-inflammatory compounds including nitric oxide (NO) are the main cause of neuro-degenerative disease such as Alzheimer's disease (AD) which is resulted in cell death. Among those pro-inflammatory compounds, NO contributes to the cell death by directly or indirectly. Methods: In the study, we examined whether ursodeoxycholic acid (UDCA), a non-toxic hydrophilic bile acid, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS). In signal transduction, we also examined the NF-${\kappa}B$ (p65/p50), IKK, and I ${\kappa}B$, which are associated with the expression of iNOS gene using western blots. Results: In the present study, we found that UDCA effectively inhibited NO production in BV-2 microglial cell, and NF-${\kappa}B$ activation was reduced by suppressing IKK gene expression and by increasing the I${\kappa}B$ in cytosol comparing those to the positive control LPS. Conclusion: Taken together, these data suggested that UDCA may playa crucial role in inhibiting the NO production and the results imply that UDCA suppresses a cue signal of the microglial activation via stimulators, such as ${\beta}$-amyloid peptides which are known to stimulate microglia in AD pathogenesis.

Keywords

References

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