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Potential Role of Ursodeoxycholic Acid in Suppression of Nuclear Factor Kappa B in Microglial Cell Line (BV-2)  

Joo, Seong-Soo (Department of Immunology, College of Pharmacy, Chung-Ang University)
Won, Tae-Joan (Department of Immunology, College of Pharmacy, Chung-Ang University)
Lee, Do-Ik (Department of Immunology, College of Pharmacy, Chung-Ang University)
Publication Information
Archives of Pharmacal Research / v.27, no.9, 2004 , pp. 954-960 More about this Journal
Abstract
Expression of the NF-$textsc{k}$B-dependent genes responsible for inflammation, such as TNF-$\alpha$, IL-1$\beta$, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer＇s disease). Although NF-$textsc{k}$B plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-$textsc{k}$B is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited I$textsc{k}$B$\alpha$ degradation to block expression of the NF-$textsc{k}$B-dependent genes in microglia when activated by $\beta$-amyloid peptide (A$\beta$). We also showed that when microglia is activated by $A\beta$42, the expression of A20 is suppressed. These findings place A20 in the category of ' protective ' genes, protecting cells from pro-inflammatory reper-toires induced in response to inflammatory stimuli in activated microglia via NF-$textsc{k}$B activation. In light of the gene and proteins for NF-$textsc{k}$B-dependent gene and inactivator for NF-$textsc{k}$B (I$textsc{k}$B$\alpha$), the observations now reported suggest that UDCA plays a role in supporting the attenuation of the production of pro-inflammatory cytokines and NO via inactivation of NF-$textsc{k}$B. Moreover, an NF-$textsc{k}$B inhibitor such as A20 can collaborate and at least enhance the anti-inflammatory effect in microglia, thus giving a potent benefit for the treatment of neurodegenerative diseases such as AD.uch as AD.
Keywords
Nuclear factor kappa B; $l{\kappa}B$$\alpha$; A20; Ursodeoxycholic acid; $\beta$-Amyloid peptide; Alzheimer's disease;
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