PURPOSE: Doxycycline has antibacterial and anti-inflammatory effects, and it also suppresses collagen biosynthesis. This study aimed to confirm the effects and mechanism of doxycycline on transforming growth factor (TGF) beta 1 induced epithelial-mesenchymal transition and cell migration in A549 and primary nasal epithelial cells. METHODS: A 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay and phalloidin-fluorescein isothiocyanate staining were used to evaluate cytotoxicity and cellular morphologic changes. Western blot and immunofluorescence staining were used to determine the expression levels of E-cadherin, vimentin, alpha-smooth muscle actin, fibronectin, phosphorylated Smad2/3, and mitogen-activated protein kinases. Scratch and transwell migration assays were used to assess cellular migration ability. RESULTS: Doxycycline (0-10 μg/mL) had no significant cytotoxic effects in A549 and primary nasal epithelial cells. Increased expression of mesenchymal markers, including vimentin, alpha-smooth muscle actin, and fibronectin in TGF beta 1 induced A549 cells were downregulated by doxycycline treatment. In contrast, E-cadherin expression was upregulated in TGF beta 1 induced A549 cells. An in vitro cell migration assay showed that doxycycline also inhibited the ability of TGF beta 1 induced migration. Doxycycline treatment suppressed the activation of Smad2/3 and p38, whereas its inhibitory effects were similar to each element-specific inhibitor in A549 and primary nasal epithelial cells. CONCLUSION: Doxycycline inhibited TGF beta 1 induced epithelial-to-mesenchymal transition and migration by targeting Smad2/3 and p38 signal pathways in respiratory epithelial cells.
Abstract 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 tr...
Last. Heung Man Lee(KU: Korea University)H-Index: 27
view all 4 authors...
Background Doxycycline has been shown to have antibacterial and anti-inflammatory effects and suppresses collagen biosynthesis. The purpose of this study was to evaluate the effects of doxycycline on transforming growth factor (TGF)-β1–induced myofibroblast differentiation and extracellular matrix production in nasal polyp–derived fibroblasts (NPDFs). We also determined the molecular mechanisms of action for doxycycline. Methods NPDFs were isolated from nasal polyps from 8 patients. Doxycycline ...
Last. Heung Man Lee(KU: Korea University)H-Index: 27
view all 4 authors...
PurposePirfenidone has been shown to have antifibrotic and anti-inflammatory effects in the lungs. The purpose of this study was to evaluate the inhibitory effects of pirfenidone on transforming growth factor (TGF)-β1-induced myofibroblast differentiation and extracellular matrix accumulation. We also determined the molecular mechanisms of pirfenidone in nasal polyp-derived fibroblasts (NPDF).MethodsNPDFs were isolated from nasal polyps from eight patients who had chronic rhinosinusitis with nas...
Last. Bing Zhou(Beijing Tongren Hospital)H-Index: 1
view all 8 authors...
Abstract Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is reported to involve different inflammatory processes in sinonasal mucosa and bone tissue, and these processes remain uncharacterized. We aimed to investigate the molecular mechanisms of osteitis in Chinese patients with CRS to better understand the pathogenesis of CRS. The study included 10 controls, 16 patients with CRSsNP, and 23 patients with CRSwNP. Ethmoid bone tissue samples were evaluated...
#1Cheol-Jung Lee(Catholic University of Korea)H-Index: 6
#2Mee-Hyun Lee(Catholic University of Korea)H-Index: 23
Last. Yong-Yeon Cho(Catholic University of Korea)H-Index: 17
view all 11 authors...
Background Magnolin is a natural compound abundantly found in Magnolia flos, which has been traditionally used in oriental medicine to treat headaches, nasal congestion and anti-inflammatory reactions. Our recent results have demonstrated that magnolin targets the active pockets of ERK1 and ERK2, which are important signaling molecules in cancer cell metastasis. The aim of this study is to evaluate the effects of magnolin on cell migration and to further explore the molecular mechanisms involved...
#1Cloé Hupin(UCL: Université catholique de Louvain)H-Index: 9
#2Sophie Gohy(UCL: Université catholique de Louvain)H-Index: 10
Last. Charles Pilette(UCL: Université catholique de Louvain)H-Index: 31
view all 6 authors...
Background: Chronic rhinosinusitis (CRS) defines a group of disorders characterized by persistent inflammation of the sinonasal tract. Epithelial changes and structural remodelling are present, but whether epithelial differentiation is altered remains uncertain. Methods: To evaluate the differentiation state of the sinonasal epithelium in CRS, sinonasal biopsies from patients with CRS with (CRSwNP) or without polyps (CRSsNP), or with allergic rhinitis (AR), as compared to controls, were processe...
Nasal polyps (NP) are one of the most common inflammatory mass lesions of the nose, affecting up to 4% of the population. They present with nasal obstruction, anosmia, rhinorrhoea, post nasal drip, and less commonly facial pain. Their etiology remains unclear, but they are known to have associations with allergy, asthma, infection, fungus, cystic fibrosis, and aspirin sensitivity. However, the underlying mechanisms interlinking these pathologic conditions to NP formation remain unclear. Also str...
Last. Nan Zhang(Ghent University Hospital)H-Index: 36
view all 9 authors...
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by both a chronic inflammation and tissue remodelling; as indicated by extracellular matrix protein deposition, basement membrane thickening, goblet cell hyperplasia and subepithelial edema, with reduced vessels and glands. Although remodelling is generally considered to be consequence of persistent inflammation, the chronological order and relationship between inflammation and remodelling in polyp development is still not clear....
The proprotein convertases (PCs) are serine proteases responsible for the proteolytic maturation of many precursor proteins involved in upper airway remodelling during nasal polyposis. We have previously found that PC1/3 is expressed in human nasal mucosa. However, whether PC1/3 is related to nasal polyp formation has not been investigated. To gain insight into the functional role of PC1/3 in nasal polyps, we determined PC1/3 expression in nasal polyps by immunostaining, Western blotting and enz...
A high-throughput small-molecule screen was conducted to identify inhibitors of epithelial–mesenchymal transition (EMT) that could be used as tool compounds to test the importance of EMT signaling in vivo during fibrogenesis. Transforming growth factor (TGF)-β1–induced fibronectin expression and E-cadherin repression in A549 cells were used as 48-hour endpoints in a cell-based imaging screen. Compounds that directly blocked Smad2/3 phosphorylation were excluded. From 2,100 bioactive compounds, m...
One of the molecular mechanisms involved in upper airway-related diseases is epithelial-to-mesenchymal transition (EMT). Olea europaea (OE) has anti-inflammatory properties and thus, great potential to prevent EMT. This study aimed to investigate the effect of OE on EMT in primary nasal human respiratory epithelial cells (RECs). Respiratory epithelial cells were isolated and divided into four groups: control (untreated), treated with 0.05% OE (OE group), EMT induced with 5 ng/ml of transforming ...