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Airway remodelling

Martina Nassif, Reindert P van Steenwijk, Jacqueline M Hogenhout, Huangling Lu, Rianne H A C M de Bruin-Bon, Alexander Hirsch, Peter J Sterk, Berto J Bouma, Bart Straver, Jan G P Tijssen, Barbara J M Mulder, Robbert J de Winter
OBJECTIVE: The association between secundum atrial septal defects (ASD) and asthma-like dyspnea with consequent long-term pulmonary inhalant use, is poorly understood in adult ASD patients. Airway hyperresponsiveness is suggested to be the underlying mechanism of cardiac asthma from mitral valve disease and ischemic cardiomyopathy. We hypothesized that airway hyperresponsiveness may also be found in adult ASD patients. Our aim was to study airway responsiveness in adult ASD patients before percutaneous closure and at short-and long-term postprocedural follow-up...
September 21, 2018: Congenital Heart Disease
Allan R Brasier
Acute exacerbations of chronic lung disease account for substantial morbidity and health costs. Repeated inflammatory episodes and attendant bronchoconstriction cause structural remodeling of the airway. Remodeling is a multicellular response to mucosal injury that results in epithelial cell state changes, enhanced extracellular deposition and expansion of pro-fibrotic myofibroblast populations. Areas covered: This manuscript overviews mechanistic studies identifying key sentinel cell populations in the airway and how pattern recognition signaling induces maladaptive mucosal changes and airway remodeling...
September 21, 2018: Expert Review of Respiratory Medicine
Takeshi Tsuda, Yohei Maeda, Masayuki Nishide, Shohei Koyama, Yoshitomo Hayama, Satoshi Nojima, Hyota Takamatsu, Daisuke Okuzaki, Yuhei Kinehara, Yasuhiro Kato, Takeshi Nakatani, Sho Obata, Hitoshi Akazawa, Takashi Shikina, Kazuya Takeda, Masaki Hayama, Hidenori Inohara, Atsushi Kumanogoh
Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis (CRS) that is characterized by intractable nasal polyp formation. Eosinophil-derived neurotoxin (EDN) is an eosinophil granule protein that is closely related to allergic inflammation, but the pathological implications of EDN in ECRS remain unknown. In this study, we evaluated the function of EDN in ECRS pathogenesis and assessed its potential as a disease activity marker. Serum EDN levels were significantly higher in patients with ECRS than in those with other nasal and paranasal diseases, and were positively correlated with clinical disease activity...
September 15, 2018: International Immunology
Bing Wei, Mingwei Sun, Yunxiao Shang, Chao Zhang, Xuyong Jiao
Background: Airway remodelling is a major contributor to hyper-responsiveness leading to chronic asthma; however, the underlying mechanisms remain unclear. This study aimed to investigate the effects of a neurokinin 1 receptor (NK1R) antagonist (WIN62577) on the migration of airway smooth muscle cells (ASMCs) and the expression of NK1R and alpha-tubulin in airway remodelling using young rats with asthma. Methods: Sprague-Dawley rats were randomly divided into a control group and airway remodelling group...
August 2018: Journal of Thoracic Disease
Anna Gungl, Valentina Biasin, Jochen Wilhelm, Andrea Olschewski, Grazyna Kwapiszewska, Leigh M Marsh
Background: Asthma is a complex chronic inflammatory disease characterised by airway inflammation, remodelling and hyperresponsiveness (AHR). Members of the AP-1 transcription factor family play important roles in the activation of the immune system and the control of cellular responses; however, their role in the development of asthma has not been well studied. We aimed to investigate the role of the lesser known AP-1 family member, Fra2 in experimental asthma. Methods: Phenotypic characterisation and gene expression profiling was performed on Fra2 (TG) overexpressing and wild-type mice...
2018: Frontiers in Immunology
Tabata M Dos Santos, Renato F Righetti, Leandro do N Camargo, Beatriz M Saraiva-Romanholo, Luciana R C R B Aristoteles, Flávia C R de Souza, Silvia Fukuzaki, Maria I C Alonso-Vale, Maysa M Cruz, Carla M Prado, Edna A Leick, Milton A Martins, Iolanda F L C Tibério
Background: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for the treatment of this disease. Objective: To study the effects of an anti-IL17 neutralizing antibody and ROCK inhibitor treatments, separately and in combination, in a murine model of chronic allergy-induced lung inflammation...
2018: Frontiers in Physiology
Richa Gupta, Giorgia Radicioni, Sabri Abdelwahab, Hong Dang, Jerome Carpenter, Michael Chua, Piotr A Mieczkowski, John Sheridan, Scott H Randell, Mehmet Kesimer
Airway epithelium structure/function can be altered by local inflammatory/immune signals, and this process is called epithelial remodeling. The mechanism by which this innate response is regulated, which causes mucin/mucus overproduction, is largely unknown. Exosomes are nano-vesicles that can be secreted and internalized by cells to transport cellular cargo, such as proteins, lipids, and miRNA. The objective of this study was to understand the role exosomes play in airway remodeling through cell-cell communication...
September 19, 2018: American Journal of Respiratory Cell and Molecular Biology
Abhijit Ricky Pal, Jean Mercer, Simon A Jones, Iain A Bruce, Brian W Bigger
INTRODUCTION: Mucopolysaccharide diseases are a group of lysosomal storage disorders caused by deficiencies of hydrolase enzymes, leading to pathological glycosaminoglycan accumulation. A number of mucopolysaccharidosis (MPS) types are characterised by severe airway disease, the aetiology of which is poorly understood. There is ongoing evidence of significant clinical disease in the long-term despite disease modifying therapeutic strategies, including enzyme-replacement therapy (ERT)...
2018: PloS One
Faith I Uwadiae, Chloe J Pyle, Simone A Walker, Clare M Lloyd, James A Harker
BACKGROUND: Allergic asthma is characterized by chronic inflammation and remodelling of the airways, associated with dysregulated type 2 immune responses and allergen-specific IgE. T follicular helper cells (TFH ) are crucial in T-dependent B cell responses and have been implicated in allergic airway disease (AAD). TFH , unlike other CD4+ T cells are uniquely reliant on continuous ICOS signalling to maintain their phenotype after T cell priming, therefore disrupting this signal can impair TFH responses...
September 16, 2018: Allergy
Dina Johar, Sameh Magdeldin
Pulmonary artery hyperplasia is the result of proliferation of the pulmonary arterial smooth muscles (PASM). Hypoxia-induced PASM proliferation in the fetus and the newborn is the primary cause of persistent pulmonary hypertension of the newborn (PPHN). This study was performed to characterize the utility of the Laser Scanning Cytometry (LSC) method in elucidating arterial cytoskeletal remodeling in an in vitro model of PPHN. The aim was to demonstrate the following: (a) LSC is a valid method for the analysis of nuclear and cytosolic fluorescence and (b) the cumulative effects of mechanical stretch together with hypoxia promote reactive oxygen species (ROS) formation...
September 13, 2018: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Ying Gao, Botao Wang, Huanan Luo, Qing Zhang, Min Xu
Aberrant proliferation and migration of airway smooth muscle cells (ASMCs) contribute to the pathogenesis of airway remodeling during asthma development. Here, the potential function of microRNA-217 (miR-217) on the cell proliferation and migration of TGF-β1-induced ASMCs and the involved mechanisms were investigated in this study. We found that miR-217 expression was apparently downregulated in a time and dose dependent characteristic in ASMCs exposed to transforming growth factor-β (TGF-β1) stimulation...
September 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Makoto Hoshino, Kenta Akitsu, Junichi Ohtawa
OBJECTIVE: Asthma often remains uncontrolled despite treatment with inhaled corticosteroids (ICS) alone or with ICS plus a long-acting β2 -agonist (LABA). The recommended alternative is the addition of either montelukast or tiotropium. The aim of this study was to compare the effects of montelukast and tiotropium on airway inflammation and remodeling in persistent asthma. METHODS: Eighty-seven patients with asthma were treated with budesonide and formoterol (640/18 μg); then, the patients were randomly allocated to three groups to receive oral montelukast (10 mg/day), inhaled tiotropium (5 μg/day), or no add-on to the maintenance therapy for 48 weeks...
September 13, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Xia Ke, Danh C Do, Changjun Li, Yilin Zhao, Marian Kollarik, Qingling Fu, Mei Wan, Peisong Gao
RATIONALE: Mesenchymal stem cells (MSCs) are increased in the airways after allergen challenge. RhoA/ROCK signaling is critical in determining the lineage fate of MSCs in tissue repair/remodeling. OBJECTIVES: To investigate the role of RhoA/ROCK signaling in lineage commitment of MSCs during allergen-induced airway remodeling and delineate the underlying mechanisms. METHODS: Active RhoA expression in asthmatic lung tissues and its role in cockroach allergen-induced airway inflammation and remodeling were investigated...
September 5, 2018: Journal of Allergy and Clinical Immunology
Sadiatu Musah, Jing Chen, Connie Schlueter, David M Humphrey, Kendall Stocke, Mona I Hoyle, Gary W Hoyle
Chlorine is a chemical threat agent that can be harmful to humans. Acute inhalation of high levels of chlorine results in the death of airway epithelial cells and can lead to persistent adverse effects on respiratory health, including airway remodeling and hyperreactivity. We previously developed a mouse chlorine exposure model in which animals developed inflammation and fibrosis in large airways. In the present study, examination by laser capture microdissection of developing fibroproliferative lesions in FVB/NJ mice exposed to 240 ppm-h chlorine revealed upregulation of genes related to macrophage function...
September 3, 2018: Toxicology and Applied Pharmacology
Jason J Gokey, John Snowball, Anusha Sridharan, Joseph P Speth, Katharine E Black, Lida P Hariri, Anne-Karina T Perl, Yan Xu, Jeffrey A Whitsett
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease causing fibrotic remodeling of the peripheral lung, leading to respiratory failure. Peripheral pulmonary epithelial cells lose normal alveolar epithelial gene expression patterns and variably express genes associated with diverse conducting airway epithelial cells, including basal cells. Single-cell RNA sequencing of pulmonary epithelial cells isolated from IPF lung tissue demonstrated altered expression of LncRNAs, including increased MEG3...
September 6, 2018: JCI Insight
Matthew G Drake, Gregory D Scott, Emily D Blum, Katherine M Lebold, Zhenying Nie, James J Lee, Allison D Fryer, Richard W Costello, David B Jacoby
In asthma, airway nerve dysfunction leads to excessive bronchoconstriction and cough. It is well established that eosinophils alter nerve function and that airway eosinophilia is present in 50 to 60% of asthmatics. However, the effects of eosinophils on airway nerve structure have not been established. We tested whether eosinophils alter airway nerve structure and measured the physiological consequences of those changes. Our results in humans with and without eosinophilic asthma showed that airway innervation and substance P expression were increased in moderate persistent asthmatics compared to mild intermittent asthmatics and healthy subjects...
September 5, 2018: Science Translational Medicine
Li-Li Liu, Yan Zhang, Xiao-Fang Zhang, Fu-Hai Li
Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects...
September 2018: Korean Journal of Physiology & Pharmacology
Alireza Shahriary, Mostafa Ghanei, Hossein Rahmani
Sulphur mustard (SM) is a powerful blister-causing alkylating chemical warfare agent used by Iraqi forces against Iran. One of the known complications of mustard gas inhalation is mustard lung which is discussed as a phenotype of chronic obstructive pulmonary disease (COPD). In this complication, there are clinical symptoms close to COPD with common etiologies, such as in smokers. Based on information gradually obtained by conducting the studies on mustard lung patients, systemic symptoms along with pulmonary disorders have attracted the attention of researchers...
November 2017: Interdisciplinary Toxicology
Shung-Te Kao, Shulhn-Der Wang, Chih-Che Lin, Li-Jen Lin
ETHNOPHARMACOLOGICAL RELEVANCE: In Asia, Jin Gui Shen Qi Wan (JGSQW) has been used for hundreds of years to treat asthma. AIM OF THE STUDY: The traditional Chinese medicine JGSQW is composed of Rehmannia glutinosa, Dioscorea opposita, Cornus officinalis, Poria cocos, Paeonia suffruticosa, Alisma orientalis, Aconitum carmichaelii and Cinnamomum cassia. However, the immunological mechanism underlying the effect of JGSQW treatment on asthma remains unclear. This study examined whether JGSQW has the potential to reduce asthma symptoms in mice with chronic asthma induced by recurrent Dermatophagoides pteronyssinus (Der p) stimulation, as well as its immunoregulatory mechanisms...
August 30, 2018: Journal of Ethnopharmacology
Hirohisa Ogawa, Masahiko Azuma, Takaaki Tsunematu, Yuuki Morimoto, Mayo Kondo, Toshifumi Tezuka, Yasuhiko Nishioka, Koichi Tsuneyama
BACKGROUND: Bronchial asthma is traditionally characterized by chronic allergic inflammation, including eosinophilia and elevated Th2 cytokines. Recently, IL-17-derived neutrophil infiltration was shown to correlate with asthma severity and airway remodeling. OBJECTIVE: To investigate the role of IL-17-derived neutrophils in airway remodeling in chronic bronchial asthma. METHODS: We utilized house dust mite antigen-induced mouse models of asthma...
September 1, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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