title: Costunolide inhibits interleukin-1beta expression by down-regulation of AP-1 and MAPK activity in LPS-stimulated RAW 264.7 cells.
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-1beta (IL-1beta) in LPS-stimulated RAW 264.7 cells. We also showed that costunolide suppressed the transcriptional activity of the IL-1beta 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-1beta gene expression and AP-1 DNA binding. Taken together, these results demonstrate that costunolide inhibits IL-1beta gene expression by blocking the activation of MAPKs and DNA binding of AP-1 in LPS-stimulated RAW 264.7 cells.
authors.affiliation: Biopotency Evaluation Laboratory, Korea Research Institute of Bioscience and Biotechnology, Taejon 305-333, Republic of Korea.
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Yeo Dae
authors.initials: YD
authors.lastname: Yoon
authors.forename: Ki Hoon
authors.initials: KH
authors.lastname: Lee
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000235:genetics; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012717:Sesquiterpenes / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D007783:Lactones
chemical_list: D015500:Chloramphenicol O-Acetyltransferase; D004247:DNA; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; D012717:Sesquiterpenes; D018808:Transcription Factor AP-1; C002602:costunolide; D007783:Lactones