title: Inhibition of TNF-α-induced MUC5AC mucin gene expression and production by wogonin through the inactivation of NF-κB signaling in airway epithelial cells.
abstract: In this study, we investigated whether wogonin significantly affects MUC5AC mucin gene expression and production in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with wogonin for 30 min and then stimulated with tumor necrosis factor-α (TNF-α) for 24 h or the indicated periods. The MUC5AC mucin gene expression and mucin protein production were measured by RT-PCR and ELISA, respectively. We found that incubation of NCI-H292 cells with wogonin significantly inhibited mucin production and down-regulated MUC5AC gene expression induced by TNF-α in a dose-dependent fashion. To elucidate the action mechanism of wogonin, effect of wogonin on TNF-α-induced NF-κB signaling pathway was investigated by western blot analysis. Wogonin inhibited NF-κB activation induced by TNF-α. Inhibition of IKK by wogonin led to the suppression of IκB phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene expression. This, in turn, led to the down-regulation of MUC5AC protein production in NCI-H292 cells. Wogonin also inhibited the gene products involved in cell survival (Bcl-2) and proliferation (cyclooxygenase-2). These results suggest that wogonin inhibits the NF-κB signaling pathway, which may explain its role in the inhibition of MUC5AC mucin gene expression and production.
authors: Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors: Md Asaduzzaman
authors: MA
authors: Sikder
authors: Hyun Jae
authors: HJ
authors: Lee
authors: Md Zakaria
authors: MZ
authors: Mia
authors: Su Hyun
authors: SH
authors: Park
authors: Jiho
authors: J
authors: Ryu
authors: Jang-Hyun
authors: JH
authors: Kim
authors: Sang Yeon
authors: SY
authors: Min
authors: Jang-Hee
authors: JH
authors: Hong
authors: Jeong Ho
authors: JH
authors: Seok
authors: Choong Jae
authors: CJ
authors: Lee
mesh_terms: D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D044950:Flavanones; D055271:Mucin 5AC; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051550:I-kappa B Kinase; C085514:wogonin
keywords: MUC5AC; NF-κB; airway mucin; wogonin