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Asthma Ipf gene

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https://www.readbyqxmd.com/read/27590145/jnk-inhibition-reduces-lung-remodeling-and-pulmonary-fibrotic-systemic-markers
#1
Jos L J van der Velden, Ying Ye, James D Nolin, Sidra M Hoffman, David G Chapman, Karolyn G Lahue, Sarah Abdalla, Peng Chen, Yong Liu, Brydon Bennett, Nasreen Khalil, Donna Sutherland, William Smith, Gerald Horan, Mahmoud Assaf, Zebulun Horowitz, Rajesh Chopra, Randall M Stevens, Maria Palmisano, Yvonne M W Janssen-Heininger, Peter H Schafer
BACKGROUND: Lung remodeling and pulmonary fibrosis are serious, life-threatening conditions resulting from diseases such as chronic severe asthma and idiopathic pulmonary fibrosis (IPF). Preclinical evidence suggests that JNK enzyme function is required for key steps in the pulmonary fibrotic process. However, a selective JNK inhibitor has not been investigated in translational models of lung fibrosis with clinically relevant biomarkers, or in IPF patients. METHODS: The JNK inhibitor CC-930 was evaluated in the house dust mite-induced fibrotic airway mouse model, in a phase I healthy volunteer pharmacodynamic study, and subsequently in a phase II multicenter study of mild/moderate IPF (n = 28), with a 4-week, placebo-controlled, double-blind, sequential ascending-dose period (50 mg QD, 100 mg QD, 100 mg BID) and a 52-week open-label treatment-extension period...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/26319446/micrornas-in-lung-diseases-recent-findings-and-their-pathophysiological-implications
#2
REVIEW
Ammar Ebrahimi, Esmaeil Sadroddiny
Lung diseases are one of the leading causes of mortality and morbidity worldwide and effective therapies are imperfect. Nonetheless, recently some novel strategies have been developed to treat and curtail their debilitating impact. Some of the treatments include the role of MicroRNAs (miRNAs) in stemming the spread of lung morbidities. Micro RNAs are small non-coding RNAs which are known as important players in the posttranscriptional regulation of gene expression in mammalian cells by regulating translation...
October 2015: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/26225835/transcriptome-meta-analysis-reveals-common-differential-and-global-gene-expression-profiles-in-cystic-fibrosis-and-other-respiratory-disorders-and-identifies-cftr-regulators
#3
Luka A Clarke, Hugo M Botelho, Lisete Sousa, Andre O Falcao, Margarida D Amaral
A meta-analysis of 13 independent microarray data sets was performed and gene expression profiles from cystic fibrosis (CF), similar disorders (COPD: chronic obstructive pulmonary disease, IPF: idiopathic pulmonary fibrosis, asthma), environmental conditions (smoking, epithelial injury), related cellular processes (epithelial differentiation/regeneration), and non-respiratory "control" conditions (schizophrenia, dieting), were compared. Similarity among differentially expressed (DE) gene lists was assessed using a permutation test, and a clustergram was constructed, identifying common gene markers...
November 2015: Genomics
https://www.readbyqxmd.com/read/26209626/the-tnf-family-molecules-light-and-lymphotoxin-%C3%AE-%C3%AE-induce-a-distinct-steroid-resistant-inflammatory-phenotype-in-human-lung-epithelial-cells
#4
Ricardo da Silva Antunes, Lisa Madge, Pejman Soroosh, Joel Tocker, Michael Croft
Lung epithelial cells are considered important sources of inflammatory molecules and extracellular matrix proteins that contribute to diseases such as asthma. Understanding the factors that stimulate epithelial cells may lead to new insights into controlling lung inflammation. This study sought to investigate the responsiveness of human lung epithelial cells to the TNF family molecules LIGHT and lymphotoxin αβ (LTαβ). Bronchial and alveolar epithelial cell lines, and primary human bronchial epithelial cells, were stimulated with LIGHT and LTαβ, and expression of inflammatory cytokines and chemokines and markers of epithelial-mesenchymal transition and fibrosis/remodeling was measured...
September 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/25410652/is-there-still-hope-for-single-therapies-how-do-we-set-up-experimental-systems-to-efficiently-test-combination-therapies
#5
REVIEW
Guy F Joos, Esteban C Gabazza
Severe asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic lung diseases with a clear need for development of new and more efficient therapy. In preclinical research, the mouse model has been instrumental in advancing our knowledge of the biology and immunology. However, it has been proven rather difficult and time consuming to develop new treatments that can impact on the clinical course of these diseases. Many challenges need to be overcome for upgrading the quality of currently available experimental disease models in order to enhance the translation rate of basic research to clinical practice...
January 2015: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/24242359/epigenetics-in-immune-mediated-pulmonary-diseases
#6
REVIEW
Yu Liu, Hui Li, Tao Xiao, Qianjin Lu
Immune-mediated pulmonary diseases are a group of diseases that resulted from immune imbalance initiated by allergens or of unknown causes. Inflammatory responses without restrictions cause tissue damage and remodeling, which leads to airway hyperactivity, destruction of alveolar architecture, and a resultant loss of lung function. Epigenetic mechanisms have been demonstrated to be involved in inflammation, autoimmunity, and cancer. Recent studies have identified that epigenetic changes also regulate molecular pathways in immune-mediated lung diseases...
December 2013: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/23590298/inflammatory-responses-of-airway-smooth-muscle-cells-and-effects-of-endothelin-receptor-antagonism
#7
Jürgen Knobloch, Yingfeng Lin, Jürgen Konradi, David Jungck, Juergen Behr, Justus Strauch, Erich Stoelben, Andrea Koch
Endothelin receptor antagonists (ETRAs), authorized for pulmonary hypertension, have failed to prove their utility in chronic lung diseases with corticosteroid-resistant airway inflammation when applied at late disease stages with emphysema/fibrosis. Earlier administration might prove effective by targeting the interaction between airway inflammation and tissue remodeling. We hypothesized that human airway smooth muscle cells (HASMCs) participate in linking inflammation with remodeling and that associated genes become differentially suppressed by ambrisentan (A-receptor selective ETRA) and bosentan (nonselective/dual ETRA)...
July 2013: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/23517647/reflections-on-micrornas-in-chronic-pulmonary-disease-looking-into-the-mir-ror-and-crystal-ball
#8
REVIEW
James G Karras, Guizhen Sun, Jia Tay, Aimee L Jackson
Chronic respiratory diseases are a significant health problem requiring novel approaches to both complement existing therapies and provide breakthrough medicines. Recent clinical advances in understanding the behavior of inhaled oligonucleotides provide the impetus for application of this technology to microRNA therapeutics. MicroRNAs are evolutionarily conserved small regulatory RNA molecules involved in tuning gene networks controlling biological and pathological processes. Deletion or overexpression of microRNAs results in phenotypic changes in animal models of disease such as cancer, fibrosis, diabetes, and inflammation...
April 2013: Inflammation & Allergy Drug Targets
https://www.readbyqxmd.com/read/23124245/changes-in-microrna-expression-in-rat-lungs-caused-by-sevoflurane-anesthesia-a-taqman%C3%A2-low-density-array-study
#9
Shunsuke Tanaka, Masashi Ishikawa, Masae Arai, Yuuki Genda, Atsuhiro Sakamoto
Reportedly, a large number of microRNAs (miRNAs) play an important role in inflammatory lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), acute respiratory distress syndrome (ARDS), and pulmonary arterial hypertension (PAH). Sevoflurane is routinely used to various patients, and its safety has been confirmed by clinical outcomes; however, its effects to lungs at the miRNA level have not been elucidated. In our previous genomic studies, we showed that sevoflurane anesthesia affected the expression of many genes and mRNAs in rat lungs...
2012: Biomedical Research
https://www.readbyqxmd.com/read/22607962/role-of-micrornas-in-lung-disease
#10
REVIEW
Martín Angulo, Emilia Lecuona, Jacob Iasha Sznajder
MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression. They actively participate in the modulation of important cell physiological processes and are involved in the pathogenesis of lung diseases such as lung cancer, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. A better understanding of the role that miRNAs play in these diseases could lead to the development of new diagnostic and therapeutic tools. In this review, we discuss the role of some miRNAs in different lung diseases as well as the possible future of these discoveries in clinical applications...
September 2012: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/22198907/genetically-manipulated-mouse-models-of-lung-disease-potential-and-pitfalls
#11
REVIEW
Rebecca M Baron, Alexander J S Choi, Caroline A Owen, Augustine M K Choi
Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease...
March 15, 2012: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/21356323/from-molecule-to-man-integrating-molecular-biology-with-whole-organ-physiology-in-studying-respiratory-disease
#12
REVIEW
Melanie Königshoff, Franziska Uhl, Reinoud Gosens
Chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF) are all characterized by structural changes of the airways and/or lungs that limit airflow and/or gas exchange. Currently, there is no therapy available that adequately targets the structural remodeling of the airways and lungs in these diseases. This underscores the great need for insight into the mechanisms that underpin the development of airway remodeling, fibrosis and emphysema in these diseases, in order to identify suitable drug targets...
October 2011: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/21029443/micrornas-in-inflammatory-lung-disease-master-regulators-or-target-practice
#13
REVIEW
Irene K Oglesby, Noel G McElvaney, Catherine M Greene
MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs with immense significance in numerous biological processes. When aberrantly expressed miRNAs have been shown to play a role in the pathogenesis of several disease states. Extensive research has explored miRNA involvement in the development and fate of immune cells and in both the innate and adaptive immune responses whereby strong evidence links miRNA expression to signalling pathways and receptors with critical roles in the inflammatory response such as NF-κB and the toll-like receptors, respectively...
2010: Respiratory Research
https://www.readbyqxmd.com/read/20082309/cytokine-dependent-balance-of-mitogenic-effects-in-primary-human-lung-fibroblasts-related-to-cyclic-amp-signaling-and-phosphodiesterase-4-inhibition
#14
Jens Selige, Hermann Tenor, Armin Hatzelmann, Torsten Dunkern
Interleukin-1beta (IL-1beta) and basic fibroblast growth factor (bFGF) are important regulators of proliferation, and their expression is increased in lungs of patients with asthma, idiopathic pulmonary fibrosis (IPF), or chronic obstructive pulmonary disease (COPD). We investigated the effect of IL-1beta and bFGF on proliferation of human lung fibroblasts and the role of COX-2, PGE(2), and cAMP in this process. Furthermore, the effect of phosphodiesterase (PDE) 3 and 4 inhibition was analyzed. In primary human lung fibroblasts low concentrations of IL-1beta (<10 pg/ml) potentiated the bFGF-induced DNA synthesis, whereas higher concentrations revealed antiproliferative effects...
May 2010: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/18760298/environmental-toxicity-redox-signaling-and-lung-inflammation-the-role-of-glutathione
#15
REVIEW
Saibal K Biswas, Irfan Rahman
Glutathione (gamma-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H(2)O(2) as a second messenger...
February 2009: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/17906365/impaired-tnfalpha-induced-vegf-expression-in-human-airway-smooth-muscle-cells-from-smokers-with-copd-role-of-mapkinases-and-histone-acetylation-effect-of-dexamethasone
#16
COMPARATIVE STUDY
Maria Raidl, Bernhard Sibbing, Justus Strauch, Katja Müller, Andre Nemat, Paul M Schneider, Haitham Hag, Erland Erdmann, Andrea Koch
The cytokine and potent angiogenic factor vascular endothelial growth factor (VEGF) plays an important role in airway remodelling in various airway diseases such as idiopathic pulmonary fibrosis, pulmonary hypertension, lung cancer, asthma and chronic obstructive pulmonary disease (COPD). The effect of cigarette-smoking on VEGF expression, the modulatory role of extracellular signal-regulated kinase (ERK)-1,-2, p38mitogen-activated protein kinase (MAPK), histone acetylation and the anti-inflammatory effect of dexamethasone on TNFalpha-induced VEGF expression were examined in human airway smooth muscle cells (HASMC) of five non-smokers, 17 smokers without airflow limitation and 15 smokers with COPD...
2007: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/17275675/genetic-mechanisms-of-susceptibility-to-oxidative-lung-injury-in-mice
#17
REVIEW
Hye-Youn Cho, Steven R Kleeberger
Genetic background is a known predisposing risk factor for many acute and chronic pulmonary disorders and responses to environmental oxidants. Variation in lung injury responses to oxidative stimuli such as ozone, particles, hyperoxia, and chemotherapeutic agents between genetically standardized inbred mouse strains has been demonstrated. In this review, we discuss quantitative trait loci (QTLs) which contain candidate genes that confer differential susceptibility to oxidative stimuli between strains in mouse models of airway toxicity and disease...
February 15, 2007: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/16005622/microsatellite-dna-instability-in-benign-lung-diseases
#18
REVIEW
Katerina Samara, Maria Zervou, Nikolaos M Siafakas, Eleni G Tzortzaki
Recently DNA mismatch repair system (MMR) has been extensively investigated in molecular medicine. Microsatellite (MS) DNA alterations are considered as indicating an ineffective MMR system. MS loss of heterozygosity (LOH) and microsatellite instability (MSI) have been reported in a number of human malignancies. LOH and MSI have recently been detected in benign diseases, such as actinic keratosis, pterygium and atherosclerosis. In addition, MSI and LOH have been detected in asthma, chronic obstructive pulmonary disease, sarcoidosis and idiopathic pulmonary fibrosis...
February 2006: Respiratory Medicine
https://www.readbyqxmd.com/read/15993846/elevated-expression-of-tarc-ccl17-and-mdc-ccl22-in-models-of-cigarette-smoke-induced-pulmonary-inflammation
#19
COMPARATIVE STUDY
Mirko Ritter, Rolf Göggel, Nveed Chaudhary, Alexander Wiedenmann, Birgit Jung, Andreas Weith, Peter Seither
TARC (CCL17) and MDC (CCL22) are well-known chemoattractants for Th2 cells. Here, we evaluated the role of both chemokines for cigarette smoke-induced airway inflammation. The expression profiles of MDC, TARC, and their receptor CCR4 were analyzed in models of acute and chronic cigarette smoke-induced airway inflammation that is characterized by a Th1 immune response. The results were compared to the expression of both chemokines in models of idiopathic pulmonary fibrosis and acute asthma, which are associated with a Th2 immune response...
August 19, 2005: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/12796054/superoxide-dismutases-in-the-lung-and-human-lung-diseases
#20
REVIEW
Vuokko L Kinnula, James D Crapo
The lungs are directly exposed to higher oxygen concentrations than most other tissues. Increased oxidative stress is a significant part of the pathogenesis of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease, parenchymal lung diseases (e.g., idiopathic pulmonary fibrosis and lung granulomatous diseases), and lung malignancies. Lung tissue is protected against these oxidants by a variety of antioxidant mechanisms among which the superoxide dismutases (SODs) are the only ones converting superoxide radicals to hydrogen peroxide...
June 15, 2003: American Journal of Respiratory and Critical Care Medicine
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