Immune Netw.  2005 Mar;5(1):45-49. 10.4110/in.2005.5.1.45.

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

• Joo SS
• Won TJ
• Hwang KW
• Lee DI

• KMID: 2150589
• DOI: http://doi.org/10.4110/in.2005.5.1.45

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 Ikappa 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 Ikappa B in cytosol comparing those to the positive control LPS. CONCLUSION: Taken together, these data suggested that UDCA may play a 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.

Keyword

Nitric oxide; iNOS; NF-kappa B; ursodeoxycholic acid; Alzheimer's disease

MeSH Terms

Alzheimer Disease
Bile
Blotting, Western
Brain
Cell Death
Cell Line*
Cues
Cytosol
Gene Expression
Inflammation
Macrophages
Microglia
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type II
Peptides
Signal Transduction
Ursodeoxycholic Acid*
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase Type II
Peptides
Ursodeoxycholic Acid