title: Emodin inhibits TNF alpha-induced MMP-1 expression through suppression of activator protein-1 (AP-1).
abstract: Matrix metalloproteinases (MMPs) are the proteases involved in the degradation of the extracellular matrix. MMP-1 is thought to be one of the key enzymes acting in fibrolysis, a process closely related to tissue remodeling. In this study, we found that emodin, an anthraquinone which has been isolated from the rhizome of Rheum palmatum, significantly inhibited TNF alpha-induced MMP-1 gene expression in a concentration-dependent manner. Therefore, we have attempted to characterize the inhibitory mechanism of emodin in TNF alpha-induced MMP-1 expression. Emodin was determined to inhibit TNF alpha-induced activation of AP-1 promoter, an important nuclear transcription factor in MMP-1 expression. Additionally, we detected that emodin suppressed the TNF alpha-induced phosphorylation of two mitogen-activated protein kinases, extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but it did not suppress the TNF alpha-induced phosphorylation of p38 kinase. In a consistent result, the TNF alpha-induced MMP-1 expression was inhibited by PD98059 (MEK/ERK inhibitor) and SP600125 (JNK inhibitor), but was not inhibited by SB203580, a p38 MAPK inhibitor. Taken together, these results show that emodin suppresses TNF alpha-induced MMP-1 expression through the inhibition of the AP-1 signaling pathway.
authors.affiliation: Biospectrum Life Science Institute, Gunpo City, Gyunggi Do, Republic of Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Lee
authors.forename: Sungran
authors.initials: S
authors.lastname: Huh
authors.forename: Cheng-Hwan
authors.initials: CH
authors.lastname: Hwang
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Cheon
authors.forename: Chang Gu
authors.initials: CG
authors.lastname: Hyun
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007231:Infant, Newborn; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D012250:Rheum / Q000737:chemistry; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1; D004642:Emodin; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one