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Asthma pathogenesis

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https://www.readbyqxmd.com/read/29454096/jak-stat-inhibitors-and-other-small-molecule-cytokine-antagonists-for-the-treatment-of-allergic-disease
#1
REVIEW
Michael D Howell, Carolyn Fitzsimons, Paul Smith
OBJECTIVE: To provide an overview of janus kinase (JAK), chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders. DATA SOURCES: PubMed literature review. STUDY SELECTIONS: Articles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their utilization in atopic dermatitis (AD), asthma, and allergic rhinitis (AR)...
February 14, 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29453280/elevated-expression-of-il-33-and-tslp-in-the-airways-of-human-asthmatics-in-vivo-a-potential-biomarker-of-severe-refractory-disease
#2
Yan Li, Wei Wang, Zhe Lv, Yun Li, Yan Chen, Kewu Huang, Chris J Corrigan, Sun Ying
The epithelial cytokines IL-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been implicated in asthma pathogenesis because they promote Th2-type cytokine synthesis, but their expression is relatively poorly documented in "real-life" human asthma. Using bronchoalveolar lavage fluid (BALF), we measured airway concentrations of these mediators and compared them with those of Th1- and Th2-type cytokines, airway infiltration of neutrophils and eosinophils, and lung function in a large group of asthmatic patients with a range of disease severity ( n = 70) and control subjects ( n = 30)...
February 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29451705/modeling-asthma-pitfalls-promises-and-the-road-ahead
#3
REVIEW
Helene F Rosenberg, Kirk M Druey
Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines...
February 16, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29451337/eosinophil-derived-exosomes-contribute-to-asthma-remodelling-by-activating-structural-lung-cells
#4
José A Cañas, Beatriz Sastre, José M Rodrigo-Muñoz, Mar Fernández-Nieto, Pilar Barranco, Santiago Quirce, Joaquín Sastre, Victoria Del Pozo
BACKGROUND: Eosinophils, a central factor in asthma pathogenesis, have the ability to secrete exosomes. However, the precise role played by exosomes in the biological processes leading up to asthma has not been fully defined. OBJECTIVE: We hypothesised that exosomes released by eosinophils contribute to asthma pathogenesis by activating structural lung cells. METHODS: Eosinophils from asthmatic patients and healthy volunteers were purified from peripheral blood, and exosomes were isolated from eosinophils of asthmatic and healthy individuals...
February 16, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29450204/ppars-key-regulators-of-airway-inflammation-and-potential-therapeutic-targets-in-asthma
#5
Asoka Banno, Aravind T Reddy, Sowmya P Lakshmi, Raju C Reddy
Asthma affects approximately 300 million people worldwide, significantly impacting quality of life and healthcare costs. While current therapies are effective in controlling many patients' symptoms, a large number continue to experience exacerbations or treatment-related adverse effects. Alternative therapies are thus urgently needed. Accumulating evidence has shown that the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors, comprising PPARα, PPARβ/δ, and PPARγ, is involved in asthma pathogenesis and that ligand-induced activation of these receptors suppresses asthma pathology...
2018: Nuclear Receptor Research
https://www.readbyqxmd.com/read/29437247/developmental-endothelial-locus-1-del-1-antagonizes-interleukin-17-mediated-allergic-asthma
#6
Shu Yan, Li Chen, Qi Zhao, Ya-Nan Liu, Rui Hou, Jing Yu, Hong Zhang
Interleukin (IL)-17 is a major contributor to the pathogenesis of allergic asthma. Developmental endothelial locus-1 (Del-1) is an endothelial cell-secreted protein known to inhibit IL-17 expression. However, little is known about the association between Del-1 and IL-17 in the pathogenesis of allergic asthma. Using bronchoalveolar Lavage Fluid (BALF) and peripheral blood samples collected from allergic asthmatic patients and controls, we explored the role of Del-1 in relation to IL-17 in allergic asthma. We found that the negative correlation between Del-1 and IL-17 was significant in BALF of allergic asthmatics...
February 13, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29434591/angiotensin-1-7-promotes-resolution-of-eosinophilic-inflammation-in-an-experimental-model-of-asthma
#7
Giselle S Magalhaes, Lívia C Barroso, Alesandra C Reis, Maria G Rodrigues-Machado, Juliana F Gregório, Daisy Motta-Santos, Aline C Oliveira, Denise A Perez, Lucíola S Barcelos, Mauro M Teixeira, Robson A S Santos, Vanessa Pinho, Maria Jose Campagnole-Santos
Defective apoptosis of eosinophils, the main leukocyte in the pathogenesis of asthma, and delay in its removal lead to lung damage and loss of pulmonary function due to failure in the resolution of inflammation. Here, we investigated the ability of angiotensin-(1-7) [Ang-(1-7)], a pivotal peptide of the renin-angiotensin system, to promote resolution of an allergic lung inflammatory response. Balb/c mice were sensitized and challenged with ovalbumin and treated with Ang-(1-7) at the peak of the inflammatory process...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29432192/cysteinyl-leukotriene-receptor-1-antagonism-prevents-experimental-abdominal-aortic-aneurysm
#8
Antonio Di Gennaro, Ana Carolina Araújo, Albert Busch, Hong Jin, Dick Wågsäter, Emina Vorkapic, Kenneth Caidahl, Per Eriksson, Bengt Samuelsson, Lars Maegdefessel, Jesper Z Haeggström
Cysteinyl-leukotrienes (cys-LTs) are 5-lipoxygenase-derived lipid mediators involved in the pathogenesis and progression of inflammatory disorders, in particular asthma. We have previously found evidence linking these mediators to increased levels of proteolytic enzymes in tissue specimens of human abdominal aortic aneurysm (AAA). Here we show that antagonism of the CysLT1 receptor by montelukast, an established antiasthma drug, protects against a strong aorta dilatation (>50% increase = aneurysm) in a mouse model of CaCl 2 -induced AAA at a dose comparable to human medical practice...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29427987/advances-and-evolving-concepts-in-allergic-asthma
#9
Hui-Ying Tung, Evan Li, Cameron Landers, An Nguyen, Farrah Kheradmand, J Morgan Knight, David B Corry
Allergic asthma is a heterogeneous disorder that defies a unanimously acceptable definition, but is generally recognized through its highly characteristic clinical expression of dyspnea and cough accompanied by clinical data that document reversible or exaggerated airway constriction and obstruction. The generally rising prevalence of asthma in highly industrialized societies despite significant therapeutic advances suggests that the fundamental cause(s) of asthma remain poorly understood. Detailed analyses of both the indoor (built) and outdoor environments continue to support the concept that not only inhaled particulates, especially carbon-based particulate pollution, pollens, and fungal elements, but also many noxious gases and chemicals, especially biologically derived byproducts such as proteinases, are essential to asthma pathogenesis...
February 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29420850/chitotriosidase-inhibits-allergic-asthmatic-airways-via-regulation-of-tgf-%C3%AE-expression-and-foxp3-treg-cells
#10
Jung Yeon Hong, Mina Kim, In Suk Sol, Kyung Won Kim, Chang-Min Lee, Jack A Elias, Myung Hyun Sohn, Chun Geun Lee
BACKGROUND: Chitotriosidase (Chitnase 1, Chit1), a major true chitinase in humans, is induced in childhood asthma and has been implicated in the pathogenesis of a variety of inflammatory and tissue remodeling responses. We hypothesized that Chit1 plays a significant role in the pathogenesis of allergic asthma. To identify the role of Chit1, the mechanisms that underlie these contributions and the relevance of these murine findings to childhood asthma. METHODS: Wild type and Chit1-deficient mice and cells in culture were used to define the roles of Chit1 in models of allergic adaptive Th2 inflammation...
February 8, 2018: Allergy
https://www.readbyqxmd.com/read/29414455/aspirin-exacerbated-respiratory-disease-current-topics-and-trends
#11
REVIEW
José Carlos Rodríguez-Jiménez, Fernanda Judith Moreno-Paz, Luis Manuel Terán, Eduardo Guaní-Guerra
Aspirin-exacerbated respiratory disease is a chronic and treatment-resistant disease, characterized by the presence of eosinophilic rhinosinusitis, nasal polyposis, bronchial asthma, and nonsteroidal anti-inflammatory drugs hypersensitivity. Alterations in arachidonic acid metabolism may induce an imbalance between pro-inflammatory and anti-inflammatory substances, expressed as an overproduction of cysteinyl leukotrienes and an underproduction of prostaglandin E2. Although eosinophils play a key role, recent studies have shown the importance of other cells and molecules in the development of the disease like mast cells, basophils, lymphocytes, platelets, neutrophils, macrophages, epithelial respiratory cells, IL-33 and thymic stromal lymphopoietin, making each of them promissory diagnostic and treatment targets...
February 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29403029/mrgprs-on-vagal-sensory-neurons-contribute-to-bronchoconstriction-and-airway-hyper-responsiveness
#12
Liang Han, Nathachit Limjunyawong, Fei Ru, Zhe Li, Olivia J Hall, Haley Steele, Yuyan Zhu, Julie Wilson, Wayne Mitzner, Marian Kollarik, Bradley J Undem, Brendan J Canning, Xinzhong Dong
Asthma, accompanied by lung inflammation, bronchoconstriction and airway hyper-responsiveness, is a significant public health burden. Here we report that Mas-related G protein-coupled receptors (Mrgprs) are expressed in a subset of vagal sensory neurons innervating the airway and mediates cholinergic bronchoconstriction and airway hyper-responsiveness. These findings provide insights into the neural mechanisms underlying the pathogenesis of asthma.
February 5, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29394345/roles-of-il-22-in-allergic-airway-inflammation-in-mice-and-humans
#13
Koichi Hirose, Takashi Ito, Hiroshi Nakajima
Asthma is a chronic inflammatory disease of the airways that is characterized by eosinophilic inflammation, mucus hypersecretion and airway remodeling that leads to airway obstruction. Although these pathognomonic features of asthma are primarily mediated by allergen-specific T helper type 2 cells (Th2 cells) and their cytokines, recent studies have revealed critical roles of lung epithelial cells in the pathogenesis of asthma. Lung epithelial cells not only form physical barriers by covering the surfaces of the airways but also sense inhaled allergens and initiate communication between the environment and the immune system...
January 31, 2018: International Immunology
https://www.readbyqxmd.com/read/29393977/itgb4-is-essential-for-containing-hdm-induced-airway-inflammation-and-airway-hyperresponsiveness
#14
Chi Liu, Lin Yuan, Yizhou Zou, Ming Yang, Yu Chen, Xiangping Qu, Huijun Liu, Jianxin Jiang, Yang Xiang, Xiaoqun Qin
Airway epithelial cells play a significant role in the pathogenesis of asthma. Although the structural and functional defects of airway epithelial cells have been postulated to increase asthma susceptibility and exacerbate asthma severity, the mechanism and implication of these defects remain uncertain. Integrin β4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. In this study, we demonstrated that ITGB4 deficiency leads to severe allergy-induced airway inflammation and airway hyper-responsiveness (AHR) in mice...
February 2, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29392055/tnf-%C3%AE-and-il-1-%C3%AE-cytokine-gene-polymorphism-in-patients-with-nasal-polyposis
#15
Onur İsmi, Cengiz Özcan, Gürbüz Polat, Seval Kul, Kemal Görür, Tuğçe Pütürgeli
Objective: Nasal Polyp (NP) is a benign mass of the paranasal sinuses that protrudes into the nasal cavity. The exact underlying pathogenesis is not known. In this study we aimed to determine the genetic susceptibility of NP formation in relation to TNF-α-308 and IL-1β-511 promoter region gene polymorphisms. Methods: A total of 71 patients with NP with asthma (n=21) or without asthma (n=50) were taken as the study group, and 91 healthy volunteers were taken as the control group...
June 2017: Turkish Archives of Otorhinolaryngology
https://www.readbyqxmd.com/read/29367592/persistent-activation-of-interlinked-type-2-airway-epithelial-gene-networks-in-sputum-derived-cells-from-aeroallergen-sensitized-symptomatic-asthmatics
#16
Anya C Jones, Niamh M Troy, Elisha White, Elysia M Hollams, Alexander M Gout, Kak-Ming Ling, Anthony Kicic, Stephen M Stick, Peter D Sly, Patrick G Holt, Graham L Hall, Anthony Bosco
Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDMS) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state...
January 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29361236/%C3%AE-arrestin-2-dependent-signaling-promotes-ccr4-mediated-chemotaxis-of-murine-t-helper-type-2-cells
#17
Rui Lin, Yeon Ho Choi, David A Zidar, Julia K L Walker
Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4+ T helper type 2 cells (Th2) are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of βarrestin-2 and that CD4+ T cells from these mice displayed significantly reduced C-C motif chemokine 22 (CCL22)-mediated chemotaxis...
January 23, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29355504/parp-1-inhibition-ameliorates-elastase-induced-lung-inflammation-and-emphysema-in-mice
#18
Vivek Dharwal, Amarjit S Naura
COPD is associated with high morbidity and mortality and no effective treatment is available till date. We have previously reported that PARP-1 plays an important role in the establishment of airway inflammation associated with asthma and ALI. In the present work, we have evaluated the beneficial effects of PARP-1 inhibition on COPD pathogenesis utilizing elastase induced mouse model of the disease. Our data show that PARP-1 inhibition by olaparib significantly reduced the elastase-induced recruitment of inflammatory cells particularly neutrophils in the lungs of mice when administered at dose of 5mg/kg b...
January 17, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29343554/biased-generation-and-in-situ-activation-of-lung-tissue-resident-memory-cd4-t-cells-in-the-pathogenesis-of-allergic-asthma
#19
Damian L Turner, Monica Goldklang, Filip Cvetkovski, Daniel Paik, Jordis Trischler, Josselyn Barahona, Minwei Cao, Ronak Dave, Nicole Tanna, Jeanine M D'Armiento, Donna L Farber
Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T cells that promote lung inflammation through recruitment of cellular effectors into the lung. A subset of lung T cells can persist as tissue-resident memory T cells (TRMs) following infection and allergen induction, although the generation and role of TRM in asthma persistence and pathogenesis remain unclear. In this study, we used a mouse model of chronic exposure to intranasal house dust mite (HDM) extract to dissect how lung TRMs are generated and function in the persistence and pathogenesis of allergic airway disease...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29342461/mechanism-of-periostin-production-in-human-bronchial-smooth-muscle-cells
#20
Kosuke Makita, Yu Mikami, Hirotaka Matsuzaki, Naoya Miyashita, Hideyuki Takeshima, Satoshi Noguchi, Masafumi Horie, Hirokazu Urushiyama, Motoyasu Iikura, Masayuki Hojo, Takahide Nagase, Yasuhiro Yamauchi
BACKGROUND: Asthma is a chronic airway inflammatory disease characterized by airway remodeling, in which the bronchial smooth muscle (BSM) cells play an important role. Periostin, a biomarker that reflects Th2-driven inflammatory diseases such as asthma, may play an important role in the asthmatic airway. Although periostin is mainly produced in airway epithelial cells and fibroblasts after interleukin (IL)-13 stimulation, whether BSM cells produce periostin remains unclear. Therefore, we investigated periostin production in BSM cells and the mechanisms involved...
January 18, 2018: International Archives of Allergy and Immunology
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