The effect of quercetin on human neutrophil elastase-induced mucin5AC expression in human airway epithelial cells.
ABSTRACT Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. Mucus hypersecretion is a common pathological change in chronic inflammatory diseases of the airway. We investigated the effect of quercetin on mucin 5AC (MUC5AC) expression induced by human neutrophil elastase (HNE) in airway epithelial cells and its molecular mechanisms. Human airway epithelial (HBE16) cells were pretreated with quercetin and were treated with HNE. We found that HNE induced a significant increase in the levels of MUC5AC and EGFR in cells treated only with HNE. Quercetin suppressed gene transcription and protein expression of MUC5AC in a dose-dependent manner, with significant inhibition from 40 μM. mRNA and protein expressions of EGFR decreased markedly when pretreated with quercetin. Among three MAPK proteins, only phosphorylated ERK1/2 protein expression increased significantly after treatment with HNE alone and decreased significantly after pretreatment with quercetin. HNE also activated phosphorylated PKC protein expression which was attenuated when pretreated with quercetin. These results suggest that quercetin can inhibit HNE-induced MUC5AC expression in human airway epithelial cells through PKC/EGFR/ERK signal transduction pathway. In the future, quercetin might be a valuable treatment for mucin hypersecretion in chronic inflammatory airway diseases in clinic.
- SourceAvailable from: Sadasivam Kaushik[Show abstract] [Hide abstract]
ABSTRACT: Mucins are O-glycosylated glycoproteins present on the apex of all wet-surfaced epithelia with a well-defined expression pattern, which is disrupted in response to a wide range of injuries or challenges. The aim of this study was to identify mucin gene sequences of gilthead sea bream (GSB), to determine its pattern of distribution in fish tissues and to analyse their transcriptional regulation by dietary and pathogenic factors. Exhaustive search of fish mucins was done in GSB after de novo assembly of next-generation sequencing data hosted in the IATS transcriptome database (www.nutrigroup-iats.org/seabreamdb). Six sequences, three categorized as putative membrane-bound mucins and three putative secreted-gel forming mucins, were identified. The transcriptional tissue screening revealed that Muc18 was the predominant mucin in skin, gills and stomach of GSB. In contrast, Muc19 was mostly found in the oesophagus and Muc13 was along the entire intestinal tract, although the posterior intestine exhibited a differential pattern with a high expression of an isoform that does not share a clear orthologous in mammals. This mucin was annotated as intestinal mucin (I-Muc). Its RNA expression was highly regulated by the nutritional background, whereas the other mucins, including Muc2 and Muc2-like, were expressed more constitutively and did not respond to high replacement of fish oil (FO) by vegetable oils (VO) in plant protein-based diets. After challenge with the intestinal parasite Enteromyxum leei, the expression of a number of mucins was decreased mainly in the posterior intestine of infected fish. But, interestingly, the highest down-regulation was observed for the I-Muc. Overall, the magnitude of the changes reflected the intensity and progression of the infection, making mucins and I-Muc, in particular, reliable markers of prognostic and diagnostic value of fish intestinal health.PLoS ONE 06/2013; 8(6):e65457. · 3.53 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Airway mucus hypersecretion is a significant clinical and pathological feature of chronic inflammatory airway diseases. Its clinical presentations include recurrent coughing and phlegm. Airway mucus is closely associated with the occurrence, development and prognosis of chronic inflammatory airway diseases and critically affects the lung function, quality of life, hospitalization rate and mortality of patients with chronic inflammatory airway diseases. Therefore, expectorant therapies targeting the potential mechanisms of mucus hypersecretion have been the focus of numerous studies. Conventional expectorants are mainly mucoactive medicines, including nausea-stimulating expectorants, mucolytics, mucokinetics, and proteases and nucleases. In addition, certain traditional Chinese herbal medicines and non-mucoactive agents, including muscarinic acetylcholine receptor antagonists, corticosteroids, leukotriene receptor antagonists and macrolide antibiotics, have also shown expectorant effects. Several novel medicines for expectorant therapy have emerged, including cholesterol-lowering statins, epidermal growth factor receptor tyrosine kinase inhibitors, phosphodiesterase-4 inhibitors, stanozolol, surfactants, flavonoids, tachykinin receptor antagonists, protease inhibitors, cytokine antagonists and purinergic agonists. With the increasing number of multidisciplinary studies, the effectiveness of expectorant therapy for the treatment of chronic inflammatory airway diseases has been confirmed. Therefore, the development of novel expectorants and the standardization of expectorant therapy are the direction and focus of future studies, thus benefiting patients who have a chronic inflammatory airway disease.Experimental and therapeutic medicine 04/2014; 7(4):763-767. · 0.94 Impact Factor