miR-223:A Key Regulator in the Innate Immune Response in Asthma and COPD

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic obstructive respiratory diseases characterized by airway obstruction, inflammation, and remodeling. Recent findings indicate the importance of microRNAs (miRNAs) in the regulation ofpathological processes involved in both diseases. MiRNAs have been implicated in a wide array of biological processes, such as inflammation, cell proliferation, differentiation, and death. MiR-223 is one of the miRNAs that is thought to play a role in obstructive lung disease as altered expression levels have been observed in both asthma and COPD. MiR-223 is a hematopoietic cell–derived miRNA that plays a role in regulation of monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses and that can be transferred to non-myeloid cells via extracellular vesicles or lipoproteins. In this translational review, we highlight the role of miR-223 in obstructive respiratory diseases, focusing on expression data in clinical samples of asthma and COPD, in vivo experiments in mouse models and in vitro functional studies. Furthermore, we provide an overview of the mechanisms by which miR-223 regulates gene expression. We specifically focus on immune cell development and activation and involvement in immune responses, which are important in asthma and COPD. Collectively, this review demonstrates the importance of miR-223 in obstructive respiratory diseases and explores its therapeutic potential in the pathogenesis of asthma and COPD. <br/

Let’s Keep in Touch:Strong Cell-cell Contacts for Healthy Lungs

Prof Irene Heijink (1975) and her team study the mechanisms underlying lung tissue damage in various lung diseases, such as asthma, COPD and pulmonary fibrosis She does this in close collaboration with the clinic, using culture models with cells derived from patients. Heijink directs the Experimental Lung Diseases Lab (EXPIRE) and is currently programme leader of the Groningen Research Institute for COPD (GRIAC), a multidisciplinary and translational research institute in which close collaboration takes place between basic and clinical scientists.Lung diseases are a major social problem. Diseases such as asthma and COPD are common and have a major impact on quality of life. In fact, COPD is currently the third box cause worldwide. Lung diseases are often only detected at a late stage when there is already significant damage that is no longer treatable. In particular, damage to the lining layer of the airways and lungs (the epithelium - involved in immune processes) with loss of mutual contact between cells in this layer is currently seen as a crucial part of disease processes. Irene Heijink discovered that an important directing role is played by the damaged epithelium in the derailed inflammatory response in the lungs of asthma and COPD patients. In her Chair in Cellular and Molecular Lung Pathology, Heijink aims to develop new strategies to repair the epithelial barrier in lung diseases and thereby stop or even reverse the disease process. In doing so, she uses advanced culture models (such as lab-on-chip), which she is developing within a large national collaboration to detect lung damage earlier and find new leads for treatment. She is also developing a new strategy in collaboration with the University of Twente, using an innovative technology, to better treat damage deep in the lungs and possibly even achieve tissue repair

miR-223 : a key regulator in the innate immune response in asthma and COPD

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic obstructive respiratory diseases characterized by airway obstruction, inflammation, and remodeling. Recent findings indicate the importance of microRNAs (miRNAs) in the regulation of pathological processes involved in both diseases. MiRNAs have been implicated in a wide array of biological processes, such as inflammation, cell proliferation, differentiation, and death. MiR-223 is one of the miRNAs that is thought to play a role in obstructive lung disease as altered expression levels have been observed in both asthma and COPD. MiR-223 is a hematopoietic cell-derived miRNA that plays a role in regulation of monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses and that can be transferred to non-myeloid cells via extracellular vesicles or lipoproteins. In this translational review, we highlight the role of miR-223 in obstructive respiratory diseases, focusing on expression data in clinical samples of asthma and COPD, in vivo experiments in mouse models and in vitro functional studies. Furthermore, we provide an overview of the mechanisms by which miR-223 regulates gene expression. We specifically focus on immune cell development and activation and involvement in immune responses, which are important in asthma and COPD. Collectively, this review demonstrates the importance of miR-223 in obstructive respiratory diseases and explores its therapeutic potential in the pathogenesis of asthma and COPD

Effects of cigarette smoking on SARS-CoV-2 receptor ACE2 expression in the respiratory epithelium(dagger)

Due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the world is currently facing high morbidity and mortality rates as well as severe disruption to normal societal and social structures. SARS-CoV-2 uses the ACE2 receptor for cellular entry. In a recent publication of The Journal of Pathology, Liu and coworkers highlight the effects of cigarette smoking on ACE2 expression in the respiratory epithelium. The authors studied the effects of acute cigarette smoke exposure in a murine model and confirmed their findings in human lung tissues and gene expression datasets. Their findings demonstrate that cigarette smoking increases ACE2 expression specifically at the apical surface of the airway epithelium. Smoking cessation resulted in lower ACE2 expression, with implications for attenuating the risk of transmission of the virus. The role of ACE2 expression in the development of COVID-19 symptoms is still under investigation, with conflicting results from experimental models on the role of ACE2 expression in SARS-CoV-2-induced lung injury. In this commentary, we highlight the implications and limitations of the study of Liu et al as well as future therapeutic strategies directed towards ACE2. (c) 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Current perspectives on the role of interleukin-1 signalling in the pathogenesis of asthma and COPD

Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality worldwide. In the context of disease pathogenesis, both asthma and COPD involve chronic inflammation of the lung and are characterised by the abnormal release of inflammatory cytokines, dysregulated immune cell activity and remodelling of the airways. To date, current treatments still only manage symptoms and do not reverse the primary disease processes. In recent work, interleukin (IL)-1α and IL-1β have been suggested to play important roles in both asthma and COPD. In this review, we summarise overwhelming pre-clinical evidence for dysregulated signalling of IL-1α and IL-1β contributing to disease pathogenesis and discuss the paradox of IL-1 therapeutic studies in asthma and COPD. This is particularly important given recent completed and ongoing clinical trials with IL-1 biologics that have had varying degrees of failure and success as therapeutics for disease modification in asthma and COPD

FIBROBLAST-SEEDED LUNG EXTRACELLULAR MATRIX (ECM)-DERIVED HYDROGELS AS AN IN VITRO MODEL FOR STROMAL BED IN IDIOPATHIC PULMONARY FIBROSIS (IPF)

Introduction: Idiopathic Pulmonary Fibrosis (IPF) is characterized by aberrant extracellular matrix (ECM) deposition and remodeling, which orchestrates cellular responses to the fibrotic microenvironment[1]. Decellularized lung ECM‐derived hydrogels resemble the mechanical properties[2] of native decellularized tissues, potentially providing a 3D model mimicking native cell‐ECM interactions. We aimed to characterize this 3D human lung microenvironment model, with respect to stiffness and viscoelastic properties, in the presence and absence of primary human lung fibroblasts.Materials &amp; Methods: Lyophilized powders of decellularized IPF and control lung matrices (pool of 6 patients) were pepsin digested, and formed to hydrogels seeded with control primary lung fibroblasts (n = 4 donors), and cultured for 14 days. Stiffness and viscoelastic relaxation were measured by Low‐Load Compression Testing[2] (20% strain).Results: IPF hydrogels were stiffer than controls (1.84 ± 0.33 kPA vs 1.37 ± 0.35 kPA), and became even more stiff when cell‐seeded (1.91 ± 0.37 kPA) in contrast to controls which became softer (1.09 ± 0.27 kPA). Time to reach 100% viscoelastic relaxation was shorter in cell‐seeded compared to native hydrogels for both IPF (19.14 ± 3.17 vs 41.6 ± 37.66 seconds) and control (11.44 ± 6.55 vs 22.21 ± 19.59 seconds).Conclusion: The mechanical properties of the ECM hydrogels were modified by fibroblasts, while in turn the ECM microenvironment altered cellular responses. These data suggest that higher stiffnesses and altered relaxation patterns of the ECM could contribute to the fibrotic response in IPF by instructing the cells. Fibroblast‐seeded ECM‐derived hydrogels can provide more insight on cell‐ECM interactions in IPF.References[1] M. W. Parker et al., “Fibrotic extracellular matrix activates a profibrotic positive feedback loop,” J. Clin. Invest., vol. 124, no. 4, pp. 1622–1635, Apr. 2014.[2] R. H. J. De Hilster et al., “Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue,” Am. J. Physiol. ‐ Lung Cell. Mol. Physiol., vol. 318, no. 4, pp. L698–L704, Apr. 2020