Potential role of ursodeoxycholic acid in suppression of nuclear factor kappa B in microglial cell line (BV-2)

Expression of the NF-κB-dependent genes responsible for inflammation, such as TNF-α, IL-1β, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer's disease). Although NF-κB plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-κB is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited IκBα degradation to block expression of the NF-κB-dependent genes in microglia when activated by β-amyloid peptide (Aβ). We also showed that when microglia is activated by Aβ42, the expression of A20 is suppressed. These findings place A20 in the category of "protective" genes, protecting cells from pro-inflammatory repertoires induced in response to inflammatory stimuli in activated microglia via NF-κB activation. In light of the gene and proteins for NF-κB-dependent gene and inactivator for NF-κB (IκBα), 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-κB. Moreover, an NF-κB 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.