Inhibition of NF-IL6 Activity by Manassantin B, a Dilignan Isolated from Saururus chinensis, in Phorbol Myristate Acetate-stimulated U937 Promonocytic Cells

  • Son, Kyung-No (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University) ;
  • Song, In-Sung (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University) ;
  • Shin, Yong-Hyun (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University) ;
  • Pai, Tong-Kun (Department of Food and Nutrition, Anyang University) ;
  • Chung, Dae-Kyun (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University) ;
  • Baek, Nam-In (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University) ;
  • Lee, Jung Joon (Anticancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Jiyoung (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University)
  • Received : 2005.03.03
  • Accepted : 2005.05.24
  • Published : 2005.08.31

Abstract

Mannasantin B, a dilignan structurally related to manssantin A, is an inhibitor of NF-${\kappa}B$ transactivation. In the present study, we found that it inhibited PMA-induced expression of IL-$1{\beta}$, IL-$1{\beta}$ mRNA, and IL-$1{\beta}$ promoter activity in U937 cells with $IC_{50}$ values of about 50 nM. It also inhibited NF-IL6- and NF-${\kappa}B$-induced activation of IL-$1{\beta}$, with $IC_{50}$ values of 78 nM and $1.6{\mu}M$, respectively, revealing a potent inhibitory effect on NF-IL6. Electrophoretic mobility shift assays showed that manassantin B had an inhibitory effect on DNA binding by NF-IL6, but not by NF-${\kappa}B$. Further analysis revealed that transactivation by NF-IL6 was also inhibited. Our results indicate that manassantin B suppresses expression of IL-$1{\beta}$ in promonocytic cells by inhibiting not only NF-${\kappa}B$ but also NF-IL6 activity. Furthermore, our observations suggest that manassantin B may be clinically useful as a potent inhibitor of NF-IL6 activity.

Keywords

$C/EBP{\beta}$;Inhibitors;Manassantin;NF-${\kappa}B$;NF-IL6;Saururus chinensis

Acknowledgement

Supported by : Korean Ministry of Agriculture

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