Ursodeoxycholic acid inhibits pro-inflammatory repertoires, IL-1 beta and nitric oxide in rat microglia.
Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread clinical use mainly for acute and chronic liver disease. Recently, treatment with UDCA in hepatic graft-versus-host disease has been given in immunosuppressive therapy for improvement of the biochemical markers of cholestasis. Moreover, it has been reported that UDCA possesses immunomodulatory effects by the suppression of cytokine production. In the present study, we hypothesized that UDCA may inhibit the production of the pro-inflammatory cytokine, IL-1beta, and nitric oxide (NO) in microglia. In the study, we found that 100 microg/mL UDCA effectively inhibited these two pro-inflammatory factors at 24 h and 48 h, compared to the Abeta42-pretreated groups. These results were compared with the LPS+UDCA group to confirm the UDCA effect. As microglia can be activated by several stimulants, such as Abeta42, in Alzheimers brain and can release those inflammatory factors, the ability to inhibit or at least decrease the production of IL-1beta and NO in Alzheimers disease (AD) is essential. Using RT-PCR, ELISA and the Griess Reagent System, we therefore found that UDCA in Abeta42 pre-treated cultures played a significant role in suppressing the expression or the production of IL-1beta and NO. Similarly, lipopolysaccharide (LPS) did not activate microglia in the presence of UDCA. Moreover, we found that UDCA exhibits a prolonged effect on microglial cells (up to 48 h), which suggests that UDCA may play an important role in chronic cell damage due to this long effect. These results further imply that UDCA could be an important cue in suppressing the microglial activation stimulated by massive Aâ peptides in the AD progressing brain.
Joo
Seong-Soo
SS
Department of Immunology, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Kang
Hee-Chul
HC
Won
Tae-Joon
TJ
Lee
Do-Ik
DI
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014580:Ursodeoxycholic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D007375:Interleukin-1; D009569:Nitric Oxide; D014580:Ursodeoxycholic Acid