Inhibition of NF-IL6 activity by manassantin B, a dilignan isolated from Saururus chinensis, in phorbol myristate acetate-stimulated U937 promonocytic cells.
Mannasantin B, a dilignan structurally related to manssantin A, is an inhibitor of NF-kappaB transactivation. In the present study, we found that it inhibited PMA-induced expression of IL-1beta, IL-1beta mRNA, and IL-1beta promoter activity in U937 cells with IC50 values of about 50 nM. It also inhibited NF-IL6- and NF-kappaB-induced activation of IL-1beta, with IC50 values of 78 nM and 1.6 microM, 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-kappaB. Further analysis revealed that transactivation by NF-IL6 was also inhibited. Our results indicate that manassantin B suppresses expression of IL-1beta in promonocytic cells by inhibiting not only NF-kappaB but also NF-IL6 activity. Furthermore, our observations suggest that manassantin B may be clinically useful as a potent inhibitor of NF-IL6 activity.
Son
Kyung-No
KN
Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University, Yongin 449-701, Korea.
Song
In-sung
IS
Shin
Yong-Hyun
YH
Pai
Tong-Kun
TK
Chung
Dae-Kyun
DK
Baek
Nam-In
NI
Lee
Jung Joon
JJ
Kim
Jiyoung
J
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D032134:Saururaceae / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D020298:U937 Cells
D022782:CCAAT-Enhancer-Binding Protein-beta; D005663:Furans; D007375:Interleukin-1; C482885:manassantin B; D013755:Tetradecanoylphorbol Acetate