Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-4-29
pubmed:abstractText
Matrix metalloproteinases (MMPs) are involved in various skin disorders, including photoaging, dermatitis, and tumorigenesis. Tumor necrosis factor (TNF)-alpha is a key proinflammatory cytokine that acts to provoke inflammation, proliferation, and tumorigenesis. The present study investigated the possible inhibitory effects of red wine polyphenols on TNF-alpha-induced upregulation of MMP-9 and on the migratory phenotype of JB6 P+ mouse epidermal (JB6 P+) cells. Red wine extract (RWE) and quercetin, which is a major flavonoid present in red wine, inhibited significantly the TNF-alpha-induced upregulation of MMP-9 and cell migration, whereas resveratrol did not have significant inhibitory effects. The inhibitory effects of RWE and quercetin were mediated by suppression of the phosphorylation of Akt and the transactivation of activator protein-1 and nuclear factor-kappaB, as determined by Western blotting and luciferase assays, respectively. Aside from Akt, quercetin had no effect on the phosphorylation of other mitogen-activated protein kinases. Direct kinase assay data revealed that RWE and quercetin inhibited phosphatidylinositol 3-kinase (PI3K) activity. The results of direct and cell-based pull-down assays demonstrated that RWE and quercetin bound to PI3K, resulting in the inhibition of PI3K activity. Using chemical inhibitors, it was confirmed that the PI3K-dependent Akt pathway was involved in TNF-alpha-induced MMP-9 upregulation and migration in JB6 P+ cells. Collectively, these results indicate that TNF-alpha-induced MMP-9 upregulation and the migratory phenotype are associated with the PI3K/Akt pathway, and that these effects are inhibited strongly by RWE and quercetin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1878-5875
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1592-600
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19401153-Animals, pubmed-meshheading:19401153-Cell Line, pubmed-meshheading:19401153-Cell Movement, pubmed-meshheading:19401153-Complex Mixtures, pubmed-meshheading:19401153-Enzyme Activation, pubmed-meshheading:19401153-Matrix Metalloproteinase 9, pubmed-meshheading:19401153-Mice, pubmed-meshheading:19401153-NF-kappa B, pubmed-meshheading:19401153-Phosphatidylinositol 3-Kinases, pubmed-meshheading:19401153-Phosphorylation, pubmed-meshheading:19401153-Protein Binding, pubmed-meshheading:19401153-Proto-Oncogene Proteins c-akt, pubmed-meshheading:19401153-Quercetin, pubmed-meshheading:19401153-Stilbenes, pubmed-meshheading:19401153-Transcription Factor AP-1, pubmed-meshheading:19401153-Transcriptional Activation, pubmed-meshheading:19401153-Tumor Necrosis Factor-alpha, pubmed-meshheading:19401153-Up-Regulation, pubmed-meshheading:19401153-Wine
pubmed:year
2009
pubmed:articleTitle
Activation of phosphatidylinositol 3-kinase is required for tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase-9: its direct inhibition by quercetin.
pubmed:affiliation
Department of Agricultural Biotechnology, Seoul National University, San 56-1, Shillim-dong, Gwanak-gu, Seoul, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't