Potential role of ursodeoxycholic acid in suppression of nuclear factor kappa B in microglial cell line (BV-2).
Expression of the NF-kappaB-dependent genes responsible for inflammation, such as TNF-alpha, IL-1beta, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer's disease). Although NF-kappaB plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-kappaB is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited IkappaB alpha degradation to block expression of the NF-kappaB-dependent genes in microglia when activated by beta-amyloid peptide (A beta). We also showed that when microglia is activated by A beta42, 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-kappaB activation. In light of the gene and proteins for NF-kappaB-dependent gene and inactivator for NF-kappaB (IkappaB 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-kappaB. Moreover, an NF-kappaB 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.
Joo
Seong Soo
SS
Department of Immunology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Won
Tae Joon
TJ
Lee
Do Ik
DI
D000818:Animals; D002460:Cell Line; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D014580:Ursodeoxycholic Acid / Q000737:chemistry / Q000494:pharmacology*
D016328:NF-kappa B; D014580:Ursodeoxycholic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse