Title | Costunolide inhibits interleukin-1β expression by down-regulation of AP-1 and MAPK activity in LPS-stimulated RAW 264.7 cells |
Authors | Jong Soon Kang; Yeo Dae Yoon; Ki Hoon Lee; Song Kyu Park; Hwan Mook Kim |
Publisher | Elsevier |
Issue Date | 2004 |
Citation | Biochemical and Biophysical Research Communications, vol. 313, no. 1, pp. 171-177 |
Keywords | AP-1; costunolide; inflammation; interleukin-1β; MAP kinase; 1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene; anthra[1,9 cd]pyrazol 6(2h) one; interleukin 1beta; transcription factor AP 1 |
Abstract | Costunolide, a sesquiterpene lactone isolated from the root of Saussurea lappa Clarke, is known to have a variety of biological activities, including anti-carcinogenic and anti-fungal activities. Here, we demonstrated the inhibitory effect of costunolide on the protein and mRNA expression of interleukin-1β (IL-1β) in LPS-stimulated RAW 264.7 cells. We also showed that costunolide suppressed the transcriptional activity of the IL-1β promoter. Moreover, costunolide inhibited the activity of AP-1 transcription factor, and the phosphorylation of MAPKs, including SAPK/JNK and p38 MAP kinase. The inhibitory effect of costunolide on AP-1 activity was also confirmed by an electrophoretic mobility shift assay. Additionally, specific inhibitors of SAPK/JNK and p38 MAP kinase, SP600125 and SB203580, also suppressed LPS-induced increase in IL-1β gene expression and AP-1 DNA binding. Taken together, these results demonstrate that costunolide inhibits IL-1β gene expression by blocking the activation of MAPKs and DNA binding of AP-1 in LPS-stimulated RAW 264.7 cells. |
ISSN | 0006-291X |
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Registered Date |
2017-04-19 |