Effect of Hepatoprotective Agents and Bile Acids on TNF-${\alpha}$ Production in Macrophage Cell Lines

간 보호제 및 담즙산류들이 마크로파지 세포주에서 TNF-${\alpha}$ 분비에 미치는 효과

  • 조재열 ((주) 대웅제약 중앙연구소) ;
  • 박지수 ((주) 대웅제약 중앙연구소) ;
  • 유은숙 ((주) 대웅제약 중앙연구소) ;
  • 백경업 ((주) 대웅제약 중앙연구소) ;
  • 박명환 ((주) 대웅제약 중앙연구소)
  • Published : 1998.02.01

Abstract

The effect of hepatoprotective agents and bile acids on tumor necrosis factor-alpha, (TNF-${\alpha}$) production in murine and human macrophage cell line (RAW264.7 and U937) was inve stigated. The hepatoprotective agents including silymarin and its major component, silybin, significantly inhibited TNF-alpha production in a concentration dependent manner ($IC_50$ of silybin=67.7${\mu}g$/ml (140.3${\mu}g$M)). In differentiated U937 cells, especially, silybin showed more effective inbitory activity ($IC_50$=35.1${\mu}g$g/ml (72.7${\mu}g$M)). These results suggest that silymarin and silybin may inhibit TNF-alpha production in the process of hepatic diseases in human. However, biphenyldimethyl dicarboxylate (DDB) was not effective. In the case of bile acids, chenodeoxycholic acid (CDCA) showed a concentration dependent inhibitory effect on TNF-alpha production ($IC_50$ of CDCA= 71.5${\mu}g$g/ml (182.1${\mu}g$M)). In contrast, glycine or taurine conjugated form (G-CDCA or T-CDCA) restored to the control level or significantly increased TNF-${\alpha}$ production. And also ursodeoxycholic acid (UDCA) and its conjugated forms (G-UDCA and T-UDCA) showed a variety of patterns on TNF-${\alpha}$ production by changes of functional groups and concentration. These results also indicate that bile acids may regulate TNF-${\alpha}$ production in normal hepatic function or disease conditions.

Keywords

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