Emodin inhibits TNF α-induced MMP-1 expression through suppression of activator protein-1 (AP-1)

• DOI: 10.1016/j.lfs.2006.08.008
• Publication Date: 2006-08-18T11:13:09Z
• Authors: Jongsung Lee; Eunsun Jung; Jiyoung Lee; Sungran Huh; Cheng-Hwan Hwang; Hwa-Young Lee; Eun-Jung Kim; Ji-Min Cheon; Chang Gu Hyun; Yeong Shik Kim; Deokhoon Park
• Keywords: Anthracenes; Flavonoids; Male; Mitogen-Activated Protein Kinase 1; 0303 health sciences; Emodin; Mitogen-Activated Protein Kinase 3; Dose-Response Relationship, Drug; Pyridines; Blotting, Western; Imidazoles; Infant, Newborn; JNK Mitogen-Activated Protein Kinases; Fibroblasts; 03 medical and health sciences; Humans; Matrix Metalloproteinase 1; Phosphorylation; Luciferases; Promoter Regions, Genetic; Rheum; Cells, Cultured

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.