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

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)
Publication Information
IMMUNE NETWORK / v.5, no.1, 2005 , pp. 45-49 More about this Journal
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
Nitric oxide; iNOS; NF-${\kappa}B$; ursodeoxycholic acid; Alzheimer's disease;
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