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Pathogenesis of COPD

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https://www.readbyqxmd.com/read/28444395/effects-of-n-acetyl-l-cysteine-on-the-membrane-vesicle-release-and-growth-of-respiratory-pathogens
#1
Charlotte Volgers, Birke J Benedikter, Gert E Grauls, Pauline H M Hellebrand, Paul H M Savelkoul, Frank R M Stassen
Bacterial infections contribute to the disease progression of chronic obstructive pulmonary disease (COPD) by stimulating mucus production in the airways. This increased mucus production and other symptoms are often alleviated when patients are treated with mucolytics such as N-acetyl-L-cysteine (NAC). Moreover, NAC has been suggested to inhibit bacterial growth. Bacteria can release membrane vesicles in response to stress and recent studies report a role for these pro-inflammatory membrane vesicles (MVs) in the pathogenesis of airways disease...
April 21, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28438639/targeting-interleukin-17-signalling-in-cigarette-smoke-induced-lung-disease-mechanistic-concepts-and-therapeutic-opportunities
#2
REVIEW
Abraham B Roos, Martin R Stampfli
It is widely accepted that compromised lung function in chronic obstructive pulmonary disease (COPD) is, at least in part, a consequence of persistent airway inflammation caused by particles and noxious gases present in cigarette smoke and indoor air pollution from burning biomass fuel. Currently, the World Health Organization estimates that 80 million people have moderate or severe COPD worldwide. While there is a global need for effective medical treatment, current therapeutic interventions have shown limited success in preventing disease pathology and progression...
April 21, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28435675/microbiome-effects-on-immunity-health-and-disease-in-the-lung
#3
REVIEW
Shakti D Shukla, Kurtis F Budden, Rachael Neal, Philip M Hansbro
Chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), are among the leading causes of mortality and morbidity worldwide. In the past decade, the interest in the role of microbiome in maintaining lung health and in respiratory diseases has grown exponentially. The advent of sophisticated multiomics techniques has enabled the identification and characterisation of microbiota and their roles in respiratory health and disease. Furthermore, associations between the microbiome of the lung and gut, as well as the immune cells and mediators that may link these two mucosal sites, appear to be important in the pathogenesis of lung conditions...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28424548/decreased-levels-of-irisin-a-skeletal-muscle-cell-derived-myokine-are-related-to-emphysema-associated-with-chronic-obstructive-pulmonary-disease
#4
Yukari Sugiyama, Kazuhisa Asai, Kazuhiro Yamada, Yuko Kureya, Naoki Ijiri, Tetsuya Watanabe, Hiroshi Kanazawa, Kazuto Hirata
BACKGROUND: Cigarette smoking-induced oxidant-antioxidant imbalance is a factor that contributes to the pathogenesis of COPD through epithelial cell apoptosis. Irisin is a skeletal muscle cell-derived myokine associated with physical activity. Irisin is also known to decrease oxidant-induced apoptosis in patients with diabetes mellitus. However, the correlation between irisin and emphysema in COPD and its role in epithelial cell apoptosis remains unknown. SUBJECTS AND METHODS: Forty patients with COPD were enrolled in this study...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28416592/-wnt-er-is-coming-wnt-signalling-in-chronic-lung-diseases
#5
H A Baarsma, M Königshoff
Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD...
April 17, 2017: Thorax
https://www.readbyqxmd.com/read/28416135/all-the-rage-in-lung-disease-the-receptor-for-advanced-glycation-endproducts-rage-is-a-major-mediator-of-pulmonary-inflammatory-responses
#6
REVIEW
Elizabeth A Oczypok, Timothy N Perkins, Tim D Oury
The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory pattern recognition receptor (PRR) that has been implicated in the pathogenesis of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells and was named for its ability to bind advanced glycation endproducts and promote vascular inflammation in the vessels of patients with diabetes. Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE's role in the lung...
March 18, 2017: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28413486/cigarette-smoke-extract-promotes-proliferation-of-airway-smooth-muscle-cells-through-suppressing-c-ebp-%C3%AE-expression
#7
Pin Guan, Wentao Cai, Huapeng Yu, Zhiyong Wu, Wei Li, Jie Wu, Juan Chen, Guangqiu Feng
Cigarette smoke has been considered a major contributor to the pathogenesis of chronic obstructive pulmonary disease (COPD). In COPD patients, the airway smooth muscle layer has been observed to be markedly thickened and the proliferation of airway smooth muscle cells (ASMCs) was therefore used by the present study as a model to assess the impact of cigarette smoke extract (CSE). ASMCs were exposed to various concentrations of CSE and the proliferation of the cells was analyzed by an MTT assay. Furthermore, the expression levels of calreticulin and CCAAT/enhancer-binding protein alpha (C/EBP-α) in CSE-stimulated ASMCs were determined by polymerase chain reaction and western blot analyses...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28410559/the-irony-of-iron-overload-and-iron-deficiency-in-chronic-obstructive-pulmonary-disease
#8
Suzanne M Cloonan, Sharon Mumby, Ian M Adcock, Augustine M K Choi, Kian Fan Chung, Gregory J Quinlan
Chronic obstructive pulmonary disease (COPD) is a debilitating inflammatory lung disease associated with cigarette smoking and is third leading cause of death worldwide. With the recent emergence of genome wide association studies (GWAS), the identification of multiple COPD susceptibility genes has enhanced and expanded our understanding of the pathogenic mechanisms associated with this debilitating lung disease. An example of such a pathogenic mechanism is the role of iron metabolism in the onset and progression of COPD...
April 14, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28408748/the-microbiome-of-the-lung-and-its-extracellular-vesicles-in-nonsmokers-healthy-smokers-and-copd-patients
#9
Hyun Jung Kim, You-Sun Kim, Kang-Hyun Kim, Jun-Pyo Choi, Yoon-Keun Kim, Sunmi Yun, Lokesh Sharma, Charles S Dela Cruz, Jae Seung Lee, Yeon-Mok Oh, Sang-Do Lee, Sei Won Lee
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, and bacterial infection plays a role in its pathogenesis. Bacteria secrete nanometer-sized extracellular vesicles (EVs), which may induce more immune dysfunction and inflammation than the bacteria themselves. We hypothesized that the microbiome of lung EVs might have distinct characteristics depending on the presence of COPD and smoking status. We analyzed and compared the microbiomes of 13 nonsmokers with normal spirometry, 13 smokers with normal spirometry (healthy smokers) and 13 patients with COPD by using 16S ribosomal RNA gene sequencing of surgical lung tissue and lung EVs...
April 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28399390/matrix-metalloproteinase-28-is-a-key-contributor-to-emphysema-pathogenesis
#10
Anne M Manicone, Sina A Gharib, Ke-Qin Gong, William E Eddy, Matthew E Long, Charles W Frevert, William A Altemeier, William C Parks, A McGarry Houghton
Chronic obstructive pulmonary disease (COPD) comprises chronic bronchitis and emphysema, and is a leading cause of morbidity and mortality. Because tissue destruction is the prominent characteristic of emphysema, extracellular proteinases, particularly those with elastolytic ability, are often considered to be key drivers in this disease. Several human and mouse studies have implicated roles for matrix metalloproteinases (MMPs), particularly macrophage-derived proteinases, in COPD pathogenesis. MMP-28 is expressed by the pulmonary epithelium and macrophage, and we have found that it regulates macrophage recruitment and polarization...
April 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28398147/salmeterol-a-long-acting-%C3%AE-2-aderenergic-receptor-agonist-inhibits-macrophage-activation-by-lipopolysaccharide-from-porphyromonas-gingivalis
#11
Monika Sharma, Lindsay Patterson, Elisha Chapman, Patrick M Flood
BACKGROUND: Salmeterol is a long-acting beta-2 adrenergic receptor (β2AR) agonist that is used to treat chronic obstructive pulmonary disease (COPD). Previously we had shown that pre-incubation of primary microglial enriched cells with Salmeterol could inhibit the inflammatory response induced by E. Coli LPS, a TLR-4 (toll-like receptor-4) agonist. In this study, we sought to determine if Salmeterol had a similar inhibitory effect on the inflammatory response of the murine macrophage cell line RAW264...
March 3, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28379462/human-metapneumovirus-infection-in-chronic-obstructive-pulmonary-disease-impact-of-glucocorticosteroids-and-interferon
#12
Keiko Kan-O, Ruben Ramirez, Martin I MacDonald, Michael Rolph, Penny A Rudd, Kirsten M Spann, Suresh Mahalingam, Philip G Bardin, Belinda J Thomas
Background.: Human metapneumovirus (hMPV) infection is implicated in exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Research into the pathogenesis of infection is restricted to animal models and information about hMPV replication and inflammatory and immune responses in human disease is limited. Methods.: Human primary bronchial epithelial cells (PBEC) from healthy, asthmatic and COPD subjects were infected with hMPV, with or without glucocorticosteroids (GCS) exposure...
April 4, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28363903/ifn-regulatory-factor-3-potentiates-emphysematous-aggravation-by-lipopolysaccharide
#13
Takashi Ishii, Keisuke Hosoki, Yuichi Nikura, Naohide Yamashita, Takahide Nagase, Naomi Yamashita
Acute exacerbation of chronic obstructive pulmonary disease (COPD) is often induced by infection and often has a poor prognosis. Bacterial LPS activates innate immune receptor TLR4 followed by activation of a transcriptional factor IFN regulatory factor-3 (IRF3) as well as NF-κB, resulting in upregulation of various inflammatory mediators. To clarify the role of IRF3 in the pathogenesis of LPS-triggered COPD exacerbation, porcine pancreatic elastase (PPE) followed by LPS was administered intranasally to wild-type (WT) or IRF3(-/-) male mice...
March 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28361885/exposure-to-ambient-particulate-matter-induced-copd-in-a-rat-model-and-a-description-of-the-underlying-mechanism
#14
Fang He, Baoling Liao, Jinding Pu, Chenglong Li, Mengning Zheng, Lingmei Huang, Yumin Zhou, Dongxing Zhao, Bing Li, Pixin Ran
While the health effects of air pollution have been an international public health concern since at least the 1950s, recent research has focused on two broad sources of air pollution, namely, biomass fuel (BMF) and motor vehicle exhaust (MVE). Many studies have shown associations between air pollution PM and exacerbations of pre-existing COPD, but the role of air pollution PM in the development and progression of COPD is still uncertain. The current study indicates that rats can develop pronounced COPD following chronic exposure to air pollution PM (BMF and MVE), as characterized by lung function reduction, mucus metaplasia, lung and systemic inflammation, emphysema, and small airway remodeling...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28352169/evidence-of-eosinophil-extracellular-trap-cell-death-in-copd-does-it-represent-the-trigger-that-switches-on-the-disease
#15
Loli Uribe Echevarría, Carolina Leimgruber, Jorge García González, Alberto Nevado, Ruth Álvarez, Luciana N García, Amado A Quintar, Cristina A Maldonado
In spite of the numerous studies on chronic obstructive pulmonary disease (COPD), the cellular and molecular basis of the disease's development remain unclear. Neutrophils and eosinophils are known to be key players in COPD. Recently, neutrophil extracellular trap cell death (NETosis), a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD. However, there is limited knowledge about eosinophil extracellular trap cell death (EETosis) and its role in the pathogenesis of COPD...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28352167/changes-in-the-number-of-cd31-cd45-sca-1-cells-and-shh-signaling-pathway-involvement-in-the-lungs-of-mice-with-emphysema-and-relevant-effects-of-acute-adenovirus-infection
#16
Minhua Deng, Jinhua Li, Ye Gan, Yan Chen, Ping Chen
BACKGROUND: COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31(-)CD45(-)Sca-1(+) cells and sonic hedgehog (Shh) signaling pathway expression levels in cigarette smoke extract (CSE)-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI)...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28349330/klotho-regulates-cigarette-smoke-induced-autophagy-implication-in-pathogenesis-of-copd
#17
Lingling Li, Min Zhang, Liqin Zhang, Yusheng Cheng, Xiongwen Tu, Zhiwei Lu
INTRODUCTION: Chronic obstructive pulmonary disease is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a fundamental cellular process that eliminates long-lived proteins and damaged organelles through lysosomal degradation pathway, though its role in human diseases remains unclear. We hypothesized that an anti-aging protein, Klotho plays an important role in regulating autophagy in response to cigarette smoke (CS)...
March 28, 2017: Lung
https://www.readbyqxmd.com/read/28347799/ursolic-acid-attenuates-cigarette-smoke-induced-emphysema-in-rats-by-regulating-perk-and-nrf2-pathways
#18
Lin Li, Yan Yin, Gang Hou, Dan Han, Jian Kang, Qiuyue Wang
OBJECTIVE: Ursolic acid (UA) is widely distributed in natural plants to against oxidation, virus, inflammation, tumor, and has been widely used in the pharmaceutical and cosmetics. However, its effect on emphysema of chronic obstructive pulmonary disease (COPD) is unknown. Unfolded protein response is involved in pathogenesis of COPD through PERK pathway. Nuclear erythroid-related factor 2 (Nrf2) regulates antioxidant defensive mechanism in COPD. This study was to explore effect and mechanism of UA on cigarette smoke (CS)-induced rat emphysema...
March 24, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28342288/the-role-of-acute-and-chronic-respiratory-colonization-and-infections-in-the-pathogenesis-of-copd
#19
REVIEW
Janice M Leung, Pei Yee Tiew, Micheál Mac Aogáin, Kurtis F Budden, Valerie Fei Lee Yong, Sangeeta S Thomas, Kevin Pethe, Philip M Hansbro, Sanjay H Chotirmall
COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses...
March 25, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28339038/lncrna%C3%A2-mediated-sirt1-foxo3a-and-sirt1-p53-signaling-pathways-regulate-type-ii-alveolar-epithelial-cell-senescence-in-patients-with-chronic-obstructive-pulmonary-disease
#20
Chao Gu, Yaqing Li, Jialiang Liu, Xiwang Ying, Yuanshun Liu, Jianping Yan, Chun Chen, Hongbin Zhou, Liming Cao, Yingyu Ma
The loss of alveolar structure and airspace enlargement are major pathological changes in chronic obstructive pulmonary disease (COPD). Type II alveolar epithelial cells (AECII) are involved in maintaining lung tissue repair and alveolar homeostasis. Long non‑coding RNAs (lncRNAs) are involved in multi‑regulating gene transcription, affecting processes including embryonic development, cell differentiation and cellular senescence. The primary aim of the present study was to explore the mechanisms of AECII senescence regulated by lncRNA‑mediated sirtuin 1 (SIRT1) and forkhead box O 3a (FoxO3a) signaling pathways in patients with COPD...
May 2017: Molecular Medicine Reports
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