scholarly journals Neutrophil Elastase and Chronic Lung Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1065
Author(s):  
Judith A. Voynow ◽  
Meagan Shinbashi
Keyword(s):  
Neutrophil Elastase ◽  
Airway Remodeling ◽  
Innate Immune ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Leukocyte Transmigration ◽  
Airway Diseases ◽  
Macrophage Phagocytosis ◽  
Mucin Expression ◽  
Cellular Apoptosis

Neutrophil elastase (NE) is a major inflammatory protease released by neutrophils and is present in the airways of patients with cystic fibrosis (CF), chronic obstructive pulmonary disease, non-CF bronchiectasis, and bronchopulmonary dysplasia. Although NE facilitates leukocyte transmigration to the site of infection and is required for clearance of Gram-negative bacteria, it also activates inflammation when released into the airway milieu in chronic inflammatory airway diseases. NE exposure induces airway remodeling with increased mucin expression and secretion and impaired ciliary motility. NE interrupts epithelial repair by promoting cellular apoptosis and senescence and it activates inflammation directly by increasing cytokine expression and release, and indirectly by triggering extracellular trap release and exosome release, which magnify protease activity and inflammation in the airway. NE inhibits innate immune function by digesting opsonins and opsonin receptors, degrading innate immune proteins such as lactoferrin, and inhibiting macrophage phagocytosis. Importantly, NE-directed therapies have not yet been effective in preventing the pathologic sequelae of NE exposure, but new therapies are being developed that offer both direct antiprotease activity and multifunctional anti-inflammatory properties.

scholarly journals Molecular Background of miRNA Role in Asthma and COPD: An Updated Insight

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Izabela Szymczak ◽  
Joanna Wieczfinska ◽  
Rafal Pawliczak
Keyword(s):  
Gene Expression Regulation ◽  
Current Knowledge ◽  
Airway Remodeling ◽  
Chronic Obstructive ◽  
Cell Type ◽  
Obstructive Pulmonary Disease ◽  
Airway Diseases ◽  
Antigen Presenting ◽  
Significant Health

Inflammatory airway diseases are a significant health problems requiring new approaches to the existing therapies and addressing fundamental issues. Difficulties in developing effective therapeutic strategies might be caused by lack of understanding of their exact molecular mechanism. MicroRNAs (miRNAs) are a class of regulators that already revolutionized the view of gene expression regulation. A cumulating number of investigations show a pivotal role of miRNAs in the pathogenesis of asthma, chronic obstructive pulmonary disease (COPD), or airway remodeling through the regulation of many pathways involved in their pathogenesis. Expression changes of several miRNAs have also been found to play a role in the development and/or improvement in asthma or COPD. Still, relatively little is known about the role of miRNAs in inflammatory disorders. The microRNA profiles may differ depending on the cell type or antigen-presenting cell. Based on the newest literature, this review discusses the current knowledge concerning miRNA contribution and influence on lung inflammation and chosen inflammatory airway diseases: asthma and COPD.

scholarly journals FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

scholarly journals Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 53
Author(s):  
Anjali Trivedi ◽  
Meraj A. Khan ◽  
Geetanjali Bade ◽  
Anjana Talwar
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Mucus Production ◽  
Obstructive Pulmonary Disease ◽  
Extracellular Traps ◽  
Endothelial Cell Death

Morbidity, mortality and economic burden caused by chronic obstructive pulmonary disease (COPD) is a significant global concern. Surprisingly, COPD is already the third leading cause of death worldwide, something that WHO had not predicted to occur until 2030. It is characterized by persistent respiratory symptoms and airway limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles of gases. Neutrophil is one of the key infiltrated innate immune cells in the lung during the pathogenesis of COPD. Neutrophils during pathogenic attack or injury decide to undergo for a suicidal death by releasing decondensed chromatin entangled with antimicrobial peptides to trap and ensnare pathogens. Casting neutrophil extracellular traps (NETs) has been widely demonstrated to be an effective mechanism against invading microorganisms thus controlling overwhelming infections. However, aberrant and massive NETs formation has been reported in several pulmonary diseases, including chronic obstructive pulmonary disease. Moreover, NETs can directly induce epithelial and endothelial cell death resulting in impairing pulmonary function and accelerating the progression of the disease. Therefore, understanding the regulatory mechanism of NET formation is the need of the hour in order to use NETs for beneficial purpose and controlling their involvement in disease exacerbation. For example, DNA neutralization of NET proteins using protease inhibitors and disintegration with recombinant human DNase would be helpful in controlling excess NETs. Targeting CXC chemokine receptor 2 (CXCR2) would also reduce neutrophilic inflammation, mucus production and neutrophil-proteinase mediated tissue destruction in lung. In this review, we discuss the interplay of NETs in the development and pathophysiology of COPD and how these NETs associated therapies could be leveraged to disrupt NETopathic inflammation as observed in COPD, for better management of the disease.

scholarly journals Targeting Cytokines as Evolving Treatment Strategies in Chronic Inflammatory Airway Diseases

2018 ◽  
Vol 19 (11) ◽  
pp. 3402 ◽  
Author(s):  
Jaleesa Garth ◽  
Jarrod Barnes ◽  
Stefanie Krick
Keyword(s):  
Clinical Trials ◽  
Allergic Asthma ◽  
Inflammatory Marker ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Bronchial Epithelium ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Airway Diseases ◽  
Novel Treatment Strategies

Cytokines are key players in the initiation and propagation of inflammation in chronic inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD), bronchiectasis and allergic asthma. This makes them attractive targets for specific novel anti-inflammatory treatment strategies. Recently, both interleukin-1 (IL-1) and IL-6 have been associated with negative health outcomes, mortality and a pro-inflammatory phenotype in COPD. IL-6 in COPD was shown to correlate negatively with lung function, and IL-1beta was induced by cigarette smoke in the bronchial epithelium, causing airway inflammation. Furthermore, IL-8 has been shown to be a pro-inflammatory marker in bronchiectasis, COPD and allergic asthma. Clinical trials using specific cytokine blockade therapies are currently emerging and have contributed to reduce exacerbations and steroid use in COPD. Here, we present a review of the current understanding of the roles of cytokines in the pathophysiology of chronic inflammatory airway diseases. Furthermore, outcomes of clinical trials in cytokine blockade as novel treatment strategies for selected patient populations with those diseases will be discussed.

scholarly journals The overlap between bronchiectasis and chronic airway diseases: state of the art and future directions

2018 ◽  
Vol 52 (3) ◽  
pp. 1800328 ◽  
Author(s):  
Eva Polverino ◽  
Katerina Dimakou ◽  
John Hurst ◽  
Miguel-Angel Martinez-Garcia ◽  
Marc Miravitlles ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Upper Airway ◽  
Airway Disease ◽  
Chronic Obstructive ◽  
Future Directions ◽  
Obstructive Pulmonary Disease ◽  
Airway Diseases ◽  
Recurrent Respiratory Infections ◽  
Sputum Production ◽  
Syndromic Approach

Bronchiectasis is a clinical and radiological diagnosis associated with cough, sputum production and recurrent respiratory infections. The clinical presentation inevitably overlaps with other respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). In addition, 4–72% of patients with severe COPD are found to have radiological bronchiectasis on computed tomography, with similar frequencies (20–30%) now being reported in cohorts with severe or uncontrolled asthma. Co-diagnosis of bronchiectasis with another airway disease is associated with increased lung inflammation, frequent exacerbations, worse lung function and higher mortality. In addition, many patients with all three disorders have chronic rhinosinusitis and upper airway disease, resulting in a complex “mixed airway” phenotype.The management of asthma, bronchiectasis, COPD and upper airway diseases has traditionally been outlined in separate guidelines for each individual disorder. Recognition that the majority of patients have one or more overlapping pathologies requires that we re-evaluate how we treat airway disease. The concept of treatable traits promotes a holistic, pathophysiology-based approach to treatment rather than a syndromic approach and may be more appropriate for patients with overlapping features.Here, we review the current clinical definition, diagnosis, management and future directions for the overlap between bronchiectasis and other airway diseases.

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