wogonin and Nasal-Polyps

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is an inflammatory sinonasal disorder characterized by eosinophilic inflammation and T-helper 2 skewing. Eosinophil accumulation in sinonasal mucosa comprises a major feature of CRSwNP. The study aimed to investigate the effect of the flavone wogonin in nasal polyposis by assessing its ability to induce eosinophil apoptosis in vitro and attenuate eosinophilic CRSwNP in mice. Double immunofluorescence, immunohistochemistry, flow cytometry, and immunoblotting were performed to evaluate hypoxia-inducible factor (HIF)-1α, survivin, and apoptotic markers in the human eosinophilic EoL-1 cell line or sinonasal tissues from patients with CRS with or without NPs. In sinonasal specimens from patients with CRS, HIF-1α and survivin were up-regulated in eosinophils from patients with NPs compared with levels in patients without NPs. Under hypoxia, HIF-1α and survivin expression was up-regulated in EoL-1 cells. Wogonin down-regulated both HIF-1α and survivin in EoL-1 cells. In addition, overexpression of survivin protected EoL-1 cells against apoptosis in response to wogonin. Moreover, wogonin attenuated nasal polyp formation in a murine model. Our findings suggest that wogonin could induce caspase-3 activation by suppressing HIF-1α and survivin expression in EoL-1 cells. Further studies regarding novel therapeutic options for CRSwNP targeting eosinophil apoptosis are needed.

Topics: Adult; Aged; Airway Remodeling; Animals; Apoptosis; Biomarkers; Caspase 3; Cell Line; Cytokines; Disease Models, Animal; Eosinophils; Female; Flavanones; Fluorescent Antibody Technique; Gene Expression; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Inflammation; Leukocyte Count; Male; Mice; Mice, Inbred BALB C; Middle Aged; Nasal Polyps; Protein Binding; Survivin

Wogonin has been shown to have antifibrotic and anti-inflammatory effects in the lower airway. The purpose of this study was to evaluate the effects of wogonin on transforming growth factor (TGF) β1-induced myofibroblast differentiation, extracellular matrix production, migration, and collagen contraction, and to determine the molecular mechanisms of wogonin in nasal polyp-derived fibroblasts (NPDF).. NPDFs were isolated from nasal polyps from eight patients. TGF-β1-induced NPDFs were treated with wogonin. Cytotoxicity was evaluated by using a 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Fibroblast migration was evaluated with transwell and scratch migration assays. The expression levels of α-smooth muscle actin, fibronectin, phosphorylated-p38, and c-Fos were determined by Western blot and/or reverse transcription-polymerase chain reaction. The total collagen amount was analyzed with the Sircol collagen assay, and contractile activity was measured by a collagen gel contraction assay.. Wogonin (0-60 μM) had no significant cytotoxic effects on TGF-β1-induced NPDFs. Migration of NPDFs was significantly inhibited by wogonin treatment. The expression levels of α-smooth muscle actin and fibronectin were significantly reduced in wogonin-treated NPDFs. Collagen production and contraction were also significantly decreased by wogonin treatment. Wogonin markedly inhibited activation of the p38/activator protein 1 pathway in TGF-β1-induced NPDFs.. These results indicated that wogonin may inhibit TGF-β1-induced myofibroblast differentiation, extracellular matrix production, migration, and collagen contraction through the p38/activator protein-1 pathway in NPDFs.

Topics: Cell Differentiation; Cell Movement; Cells, Cultured; Extracellular Matrix; Fibroblasts; Flavanones; Humans; Myofibroblasts; Nasal Polyps; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Transcription Factor AP-1; Transforming Growth Factor beta1