Inhibitory Effect of Delphinidin on Extracellular Matrix Production via the MAPK/NF-kappaB Pathway in Nasal Polyp-Derived Fibroblasts

ABSTRACT

PURPOSE: Nasal polyps are associated with chronic inflammation of the mucous membranes in the nose and paranasal sinuses and involved in extracellular matrix (ECM) accumulation. Delphinidin promotes ECM degradation in hepatitis and cardiac fibrosis. The aims of this study were to examine the inhibitory effect of delphinidin on TGF-beta1-induced myofibroblast differentiation and ECM accumulation, and to determine the underlying mechanisms in nasal polyp-derived fibroblasts (NPDFs). METHODS: NPDFs were stimulated with TGF-beta1, with or without delphinidin, and the expression levels of alpha-SMA, fibronectin, and collagen type I were determined by RT-PCR, Western blot analysis, and collagen assay. The expression of alpha-SMA protein was measured by immunocytochemical staining. Mitogen-activated protein kinase and NF-kappaB activation induced by TGF-beta1 were determined by Western blot analysis. The transcriptional activity of NF-kappaB was measured by luciferase assay. RESULTS: The expression levels of alpha-SMA, fibronectin, and collagen type I increased in TGF-beta1-stimulated NPDFs. In TGF-beta1-induced NPDFs, delphinidin inhibited the expression of alpha-SMA, fibronectin, and collagen. Inhibitors of MAPK and NF-kappaB blocked the expression of alpha-SMA, fibronectin, and collagen type I. Delphinidin suppressed the activation of MAPK and NF-kappaB induced by TGF-beta1 stimulation. CONCLUSIONS: These results suggest that delphinidin may inhibit TGF-beta1-induced myofibroblast differentiation and ECM production through the MAPK/NF-kappaB signaling pathway in NPDFs.