Michael Roth's research while affiliated with Universitätsspital Basel and other places

Publications (247)

Article
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Background: Cigarette smoke is assumed to cause the loss of airway wall structure in chronic obstructive pulmonary disease (COPD) by reducing airway smooth muscle cell (ASMC) function. It also modifies mTOR activity, microRNA (miR)-101-3p expression, and mitochondria function. Here, the link between miR-101-3p and mTOR-regulated mitochondria integ...
Article
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Chronic obstructive pulmonary disease (COPD) is characterized by irreversible deterioration of the airway wall. Cigarette smoking is the major trigger, and in vitro studies showed that cigarette smoke extract (CSE) induced mitophagy in airway epithelial cells via oxidative stress, but this mechanism was not studied in airway smooth muscle cells (AS...
Article
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Lower respiratory tract infections caused over 4 million deaths per year worldwide, especially in low-income countries. Viral respiratory infections often occur as rapidly spreading seasonal endemic or epidemic, and sometimes due to new respiratory viruses including corona viruses. The first level of host defense against viral infection is based on...
Article
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Airway wall remodeling is a pathology occurring in chronic inflammatory lung diseases including asthma, chronic obstructive pulmonary disease, and fibrosis. In 2017, the American Thoracic Society released a research statement highlighting the gaps in knowledge and understanding of airway wall remodeling. The four major challenges addressed in this...
Article
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In clinical studies, OM-85 Broncho-Vaxom®, a bacterial lysate, reduced viral respiratory tract infection. Infection of epithelial cells by SARS-CoV-2 depends on the interaction of its spike-protein (S-protein) with host cell membrane proteins. In this study, we investigated the effect of OM-85 on the expression of S-protein binding proteins by huma...
Article
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Idiopathic pulmonary fibrosis (IPF) is a progressive terminal lung disease, and therapies aim to block fibrosis. Fibroblast proliferation is controlled by C/EBP-β, microRNA cluster 17-92 (miR17-92), and Erk1/2 mitogen-activated protein kinase. This study assessed the role of miR17-92 in IPF-fibroblast proliferation and its modification by treprosti...
Article
Airway epithelial mitochondrial oxidative stress and damage is an important pathology in chronic obstructive pulmonary disease (COPD). Mitophagy involves MAPK15-ULK1 signaling, the role of which is unknown in COPD. This study investigated MAPK15-ULK1 signaling in airway epithelial cells of COPD patients and its activation by cigarette smoke extract...
Article
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Background: Bronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes. Methods: Endobronchial biopsies (n = 450) were collected from 30 patient...
Article
Background Increased airway smooth muscle mass is a key pathology in asthma. Bronchial thermoplasty is a treatment for severe asthma based on selective heating of the airways that aims to reduce the mass of airway smooth muscle cells (ASMC), and thereby bronchoconstriction. However, short heat exposure is insufficient to explain the long-lasting ef...
Article
Background Fasting changes mitochondrial function, and mTOR acts as a major regulator of mitochondrial energy production ensuring the survival under reduced supply of nutrition. This study assessed the role of protein arginine methyltransferase 1 (PRMT1), which regulates mitochondrial function, in the context of fasting. Methods The effect of fast...
Article
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EPs®7630, extracted from Pelargonium sidoides, reduces the severity of viral upper respiratory tract infections. Vitamin D also improves anti-viral host defense through similar signaling pathways. This study assessed if EPs®7630 modifies vitamin D receptor (VDR) expression and function by human bronchial epithelial cells. Bronchial epithelial cells...
Article
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Oral bacterial lysates (OBLs) can reduce the frequency and severity of recurrent respiratory tract infections in children from viral and bacterial origins. OBL-induced early innate immune reaction was already shown, but the specific features of different OBLs have never been studied and compared. A study was conducted to assess in vitro the protect...
Preprint
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Background: The Pelargonium sidoides herbal drug preparation EPs®7630 reduces the severity of viral upper respiratory tract infections. Vitamin D a secosteroid also improves anti-viral host defence. The anti-viral effect of both compounds was linked to similar signalling pathways in immune and epithelial cells. This study assessed if EPs®7630 modif...
Article
Protein arginine methyltransferase-1 (PRMT1) is an important epigenetic regulator of cell function and contributes to inflammation and remodeling in asthma in a cell type-specific manner. Disease-specific expression patterns of microRNAs (miRNA) are associated with chronic inflammatory lung diseases, including asthma. The de novo synthesis of miRNA...
Article
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In healthy infants and young children, the development of respiratory tract infections (RTIs) is extremely common. In this paper, we present an international consensus of the available approaches for the prevention of recurrent RTIs in children, including the atopic/allergic ones as well as those with asthma. Few convincing measures for reducing th...
Article
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Mitochondrial damage in airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Sirtuin 3 (Sirt3) is a mitochondrial deacetylase regulating mitochondrial function, but its role in the pathogenesis of COPD is still unknown. The aim of the present study was to investigate the effect of Sirt...
Article
Bronchial thermoplasty (BT) is to date the only therapy, which lastingly reduces airway wall remodelling. However, the mechanism of action of BT is not well understood. This study aimed to characterise the changes of remodelling regulating signalling pathways by BT in asthma. Bronchial alveolar lavage fluid (BALF) was obtained from eight patients w...
Article
Purpose: Adrenomedullin (AM) is a pluripotent peptide hormone with contradictory effects in human health and disease. In chronic inflammatory lung diseases, such as asthma and COPD, AM has been shown to inhibit inflammation and cell proliferation. In the present study, we aimed to investigate the effect of AM on pro-angiogenic and pro-inflammatory...
Article
The deregulated cross‐talk between airway epithelial cells with subepithelial fibroblasts during inflammation drives the pathogenesis of asthma. Bioinformatics analysis and luciferase activity assay suggested that B cell lymphoma‐2 (BCL2) and CXC ligand 12 (CXCL12) are potential targets of miR‐23a. The aim of this study was to elucidate the effect...
Article
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Remodelling of the peripheral lung tissue and fibrotic foci are the main pathologies of idiopathic pulmonary fibrosis (IPF), a disease that is difficult to treat. TGF- β activation of peripheral lung fibroblasts is indicated as the major cause of tissue remodelling in IPF and is resulting in fibroblast hyperplasia and deposition of extracellular ma...
Article
Airway smooth muscle cell (ASMC) hyperplasia causes airway wall remodelling, which is resisting to therapy. Long acting β2-agonists (LABA) relax airway muscles, but their effect on remodelling is unclear. This study compared the anti-proliferative effect of LABA in human primary ASMC, in situations where LABA were applied before, together, or after...
Article
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The patho-mechanism leading to airway wall remodeling in allergic asthma is not well understood and remodeling is resistant to therapies. This study assessed the effect of immunoglobulin E (IgE) in the absence of allergens on human primary airway smooth muscle cell (ASMC) remodeling in vitro. ASMCs were obtained from five allergic asthma patients a...
Data
Figs (A) Phase-contrast microscopy of primary human bronchial epithelial cells. Epithelial cells show knobble-stone phenotype (day 0). EPs 7630 alone, second row, did not alter the phenotype over 2 days; while RV16 infection significantly reduced cell numbers (3rd row, 1st photograph). When pre-incubated for 1 day with EPs 7630 cell survival was in...
Article
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Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides...
Data
Tables A and B: Optical density values derived from Fig C by image analysis (imageJ). Data is shown for the same patients shown in S2 File. Mean, S.D. and S.E.M. as well as Student’s t-test were performed by Excel program. Fig C: Representative Western-blots of ICOS and ICOSL. Protein bands used to calculate optical density values presented in Tabl...
Data
Table A: Optical density values for SOCS1 obtained by cell based ELISA in the same patients shown in S2 File. Mean, S.D. and S.E.M. as well as Student’s t-test were performed by Excel program. (PDF)
Data
Table A: Optical density values derived from Fig B by image analysis (imageJ). Data is shown for the same patients shown in S2 File. Mean, S.D. and S.E.M. as well as Student’s t-test were performed by Excel program. Fig B: Representative Western-blots of C1qR. Protein bands used to calculate optical density values presented in Table A are marked by...
Data
Table A: Number of surviving human bronchial epithelial cells after RV16 infection for 6 healthy controls (H01-H06), 6 asthma patients (A01-A06), and 6 COPD patients (CD01-CD06). Table B: Number of RV16 infected cells for the same patients presented in table A. Mean, S.D. and S.E.M. as well as Student’s t-test were performed by Excel program. (PDF)
Data
Table A: Optical density values derived from Fig B by image analysis (imageJ). Data is shown for the same patients shown in S2 File. Mean, S.D. and S.E.M. as well as Student’s t-test were performed by Excel program. Fig B: Representative Western-blots of β-defensin1. Protein bands used to calculate optical density values presented in Table A are ma...
Article
Hyaluronic acid (HA) and its degradation products play an important role in lung pathophysiology and airway remodelling in chronic obstructive pulmonary disease (COPD).We investigated if HA and its degrading enzyme hyaluronidase (HYAL)-1 are associated with COPD severity and outcome.Serum HA was assessed in a discovery cohort of 80 COPD patients at...
Article
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Tissue remodeling of subepithelial mesenchymal cells is a major pathologic condition of chronic obstructive pulmonary disease and asthma. Fibroblasts contribute to fibrotic events and inflammation in both airway diseases. Recent mechanistic studies established a link between mitochondrial dysfunction or aberrant biogenesis leading to tissue remodel...
Article
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Silica particles induce lung inflammation and fibrosis. Here we show that stimulator of interferon genes (STING) is essential for silica-induced lung inflammation. In mice, silica induces lung cell death and self-dsDNA release in the bronchoalveolar space that activates STING pathway. Degradation of extracellular self-dsDNA by DNase I inhibits sili...
Article
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Background Type II alveolar epithelial cells (AT2) play a pivotal role in maintaining the integrity and function of the alveoli. Only recently, the role of impaired epithelial repair mechanisms after injury in the pathogenesis of idiopathic pulmonary fibrosis has been demonstrated, and has shifted the AT2 cell in the focus of interest. Therefore, u...
Data
Statistical significant results for the presented data in Figs 2, 4 and 5. (DOCX)
Article
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Treprostinil is applied for pulmonary arterial hypertension (PAH) therapy. However, the mechanism by which the drug achieves its beneficial effects in PAH vessels is not fully understood. This study investigated the effects of treprostinil on PDGF-BB induced remodelling parameters in isolated human pulmonary arterial smooth muscle cells (PASMC) of...
Article
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Background: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? Methods: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and...
Article
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Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-β1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-...