Estudios científicos
Activation of phosphatidylinositol 3-kinase is required for tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase-9: its direct inhibition by quercetin.
Abstract:
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.
Comentarios divulgativos:
Las metaloproteinasas de la matriz están involucradas en carios tipos de enfermedades en la piel como la dermatitis y la tumorogénesis. El factor necrótico alfa de los tumores (TNF-alpha) es una citosina inflamatoria que actua provovcando la inflamación, proliferación y tumorogénesis. El siguiente estudio investiga los posibles efectos inhibitorios de los polifenoles del vino tinto en la regulación del factor TNF-alfa. El extracto de vino tinto (RWE) y la quecercita el cual es el mayor flavonoide presente en el vino tinto, inhiben significativamente al TNF-alfa induciendo la regulación de MMP-9 y la migración celular. Sin embargo el resveratrol no tiene efectos inhibitorios significativos. En resumen estos resultados indican que el TNF-alfa induce la regulación de MMP-9 y el fenotipo migratorio asociado con la ruta PI3K/Akt y estos efectos están inhibidos por RWE y quecertina
