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https://www.readbyqxmd.com/read/27906453/syk-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling-in-mice
#1
Christoph Tabeling, Julia Herbert, Andreas C Hocke, David Lamb, Lutz Wollin, Klaus Erb, Ekaterina Boiarina, Hesam Movassagh, Jörg Scheffel, Jan M Doehn, Stefan Hippenstiel, Marcus Maurer, Abdelilah S Gounni, Wolfgang M Kuebler, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
https://www.readbyqxmd.com/read/27905842/airway-smooth-muscle-cells-from-ovalbumin-sensitized-mice-show-increased-proliferative-response-to-tgf%C3%AE-1-due-to-up-regulation-of-smad3-and-tgf%C3%AE-rii
#2
Jianting Shi, Ming Chen, Lihua Ouyang, Linjie Huang, Xiaoling Lin, Wei Zhang, Ruiyun Liang, Zhiqiang Lv, Shanying Liu, Shanping Jiang
Transforming growth factor (TGF)-β1 is an important cytokine in airway remodeling in asthma. However, results of studies focusing on the effect of TGFβ1 on proliferation of airway smooth muscle cells (ASMCs) are controversial. This study aimed to elucidate the role of TGFβ1 signaling in the proliferation of ASMCs by establishing an allergic model that mimics airway remodeling in chronic asthma and cell culture. Cell proliferation was detected by viable cell counting and Cell Counting Kit (CCK)-8 analysis...
December 1, 2016: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/27905542/defining-an-olfactory-receptor-function-in-airway-smooth-muscle-cells
#3
William H Aisenberg, Jessie Huang, Wanqu Zhu, Premraj Rajkumar, Randy Cruz, Lakshmi Santhanam, Niranjana Natarajan, Hwan Mee Yong, Breann De Santiago, Jung Jin Oh, A-Rum Yoon, Reynold A Panettieri, Oliver Homann, John K Sullivan, Stephen B Liggett, Jennifer L Pluznick, Steven S An
Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27887617/increased-expression-of-trop2-in-airway-basal-cells-potentially-contributes-to-airway-remodeling-in-chronic-obstructive-pulmonary-disease
#4
Qixiao Liu, Haijun Li, Qin Wang, Yuke Zhang, Wei Wang, Shuang Dou, Wei Xiao
BACKGROUND: The airway epithelium of chronic obstructive pulmonary disease (COPD) patients undergoes aberrant repair and remodeling after repetitive injury following exposure to environmental factors. Abnormal airway regeneration observed in COPD is thought to originate in the stem/progenitor cells of the airway epithelium, the basal cells (BCs). However, the molecular mechanisms underlying these changes remain unknown. Here, trophoblast cell surface antigen 2 (TROP2), a protein implicated in the regulation of stem cell activity, was examined in lung tissue samples from COPD patients...
November 25, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27886853/airway-remodeling-associated-with-cough-hypersensitivity-as-a-consequence-of-persistent-cough-an-experimental-study
#5
Hitoshi Nakaji, Akio Niimi, Hirofumi Matsuoka, Toshiyuki Iwata, Shilei Cui, Hisako Matsumoto, Isao Ito, Tsuyoshi Oguma, Kojiro Otsuka, Tomoshi Takeda, Hideki Inoue, Tomoko Tajiri, Tadao Nagasaki, Yoshihiro Kanemitsu, Kazuo Chin, Michiaki Mishima
BACKGROUND: Chronic cough involves airway remodeling associated with cough reflex hypersensitivity. Whether cough itself induces these features remains unknown. METHODS: Guinea pigs were assigned to receive treatment with citric acid (CA), saline (SA), or CA+dextromethorphan (DEX). All animals were exposed to 0.5M CA on days 1 and 22. On days 4-20, the CA and CA+DEX groups were exposed to CA, and the SA group to saline thrice weekly, during which the CA+DEX group was administered DEX pretreatment to inhibit cough...
November 2016: Respiratory Investigation
https://www.readbyqxmd.com/read/27878968/proprotein-convertase-inhibition-promotes-ciliated-cell-differentiation-a-potential-mechanism-for-the-inhibition-of-notch1-signalling-by-decanoyl-rvkr-chloromethylketone
#6
Sang-Nam Lee, In-Suk Choi, Hyun Jun Kim, Eun Jin Yang, Hyun Jin Min, Joo-Heon Yoon
Chronic repetitive rounds of injury and repair in the airway lead to airway remodelling, including ciliated cell loss and mucous cell hyperplasia. Airway remodelling is mediated by many growth and differentiation factors including Notch1, which are proteolytically processed by proprotein convertases (PCs). The present study evaluated a novel approach for controlling basal cell-type determination based on the inhibition of PCs. It was found that decanoyl-RVKR-chloromethylketone (CMK), a PC inhibitor, promotes ciliated cell differentiation and has no effect on the ciliary beat frequency in air-liquid interface (ALI) cultures of human nasal epithelial cells (HNECs)...
November 22, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27878686/role-of-anti-inflammatory-cytokines-il-35-and-il-37-in-asthma
#7
REVIEW
Daiju Hu
Asthma is a chronic airway inflammation that is characterized by intense eosinophil infiltrates, mucus hypersecretion, airway remodeling, and airway hyperresponsiveness. Interleukin (IL)-35 and IL-37 are two cytokines with anti-inflammatory effects found in immune response. Recent findings suggested that expressions of IL-35 and IL-37 are abnormal in asthma. Functional analysis further confirmed the important roles of them in the pathogenesis of asthma. The present study reviewed the updated evidence indicating the roles of IL-35 and IL-37 in asthma...
November 23, 2016: Inflammation
https://www.readbyqxmd.com/read/27875656/involvement-of-jnk-in-tnf%C3%AE-driven-remodelling
#8
Irene Mj Eurlings, Niki L Reynaert, Cheryl van de Wetering, Scott W Aesif, Evi M Mercken, Rafael de Cabo, Jos L van der Velden, Yvonne M Janssen-Heininger, Emiel F M Wouters, Mieke A Dentener
Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) is characterized by airway wall thickening and/or emphysema. Although the bronchial and alveolar compartments are functionally independent entities, we recently showed comparable alterations in matrix composition comprised of decreased elastin content and increased collagen and hyaluronan contents of alveolar and small airway walls. Out of several animal models tested SPC-TNFα mice showed remodelling in alveolar and airway walls similar to what is observed in COPD patients...
November 22, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27867544/a-morphologic-study-of-the-airway-structure-abnormalities-in-patients-with-asthma-by-high-resolution-computed-tomography
#9
Dan Wang, Jian Luo, Wen Du, Lan-Lan Zhang, Li-Xiu He, Chun-Tao Liu
BACKGROUND: Airway structure changes, termed as airway remodeling, are common in asthma patients due to chronic inflammation, which can be assessed by high-resolution computed tomography (HRCT). Considering the controversial conclusions in the correlation of morphologic abnormalities with clinical feature and outcome, we aimed to further specify and evaluate the structural abnormalities of Chinese asthmatics by HRCT. METHODS: From August 2012 to February 2015, outpatients with asthma were recruited consecutively in the Asthma Center of West China Hospital, Sichuan University...
October 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27866296/intranasal-curcumin-inhibits-pulmonary-fibrosis-by-modulating-matrix-metalloproteinase-9-mmp-9-in-ovalbumin-induced-chronic-asthma
#10
Preeti S Chauhan, D Dash, Rashmi Singh
Pulmonary fibrosis is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Intranasal curcumin, an anti-inflammatory molecule, has been found effective in allergic asthma. To study the effect of intranasal curcumin on airway remodeling and fibrosis in murine model of chronic asthma, BALB/c mice were sensitized to ovalbumin (OVA) and exposed to OVA aerosol (2%) from day 21 (after sensitization) for 5 weeks (twice/week)...
November 19, 2016: Inflammation
https://www.readbyqxmd.com/read/27858144/th9-and-other-il-9-producing-cells-in-allergic-asthma
#11
REVIEW
Sonja Koch, Nina Sopel, Susetta Finotto
Allergic asthma is a worldwide increasing chronic disease of the airways which affects more than 300 million people. It is associated with increased IgE, mast cell activation, airway hyperresponsiveness (AHR), mucus overproduction and remodeling of the airways. Previously, this pathological trait has been associated with T helper type 2 (Th2) cells. Recently, different CD4(+) T cell subsets (Th17, Th9) as well as cells of innate immunity, like mast cells and innate lymphoid cells type 2 (ILC2s), which are all capable of producing the rediscovered cytokine IL-9, are known to contribute to this disease...
November 17, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27854509/tgf-%C3%A3-1-function-in-airway-remodeling-and-hyperresponsiveness-the-missing-link
#12
Christie A Ojiaku, Edwin J Yoo, Reynold A Panettieri
The pathogenesis of asthma includes a complex interplay between airway inflammation, hyperresponsiveness, and remodeling. Current evidence suggests that airway structural cells - including bronchial smooth muscle cells, myofibroblasts, fibroblasts, and epithelial cells -mediate all three aspects of asthma pathogenesis. While studies show a connection between airway remodeling and changes in bronchomotor tone, the relationship between the two remains unclear. Transforming growth factor beta 1 (TGF-ß1), a growth factor elevated in the airway of patients with asthma, plays a role in airway remodeling and the shortening of various airway structural cells...
November 17, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27847210/targeted-inhibition-of-six1-attenuates-allergic-airway-inflammation-and-remodeling-in-asthmatic-mice
#13
Zhao-Chuan Yang, Ming-Ji Yi, Yan-Chun Shan, Chong Wang, Ni Ran, Li-Ying Jin, Peng Fu, Xue-Ying Feng, Lei Xu, Zheng-Hai Qu
Asthma is an inflammatory disease of the airways, characterized by lung eosinophilia, mucus hypersecretion by goblet cells and airway hyperresponsiveness to inhaled allergens. The purpose of this study was to evaluate the effects of Six1 on airway inflammation and remodeling and the underlying mechanisms in a murine model of chronic asthma. Female BALB/c mice were randomly divided into four groups: phosphate-buffered saline control, ovalbumin (OVA)-induced asthma group, OVA+siNC and OVA+siSix1. In this mice model, Six1 expression level was significantly elevated in OVA-induced asthma of mice...
November 12, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27837271/airway-remodelling-in-the-transplanted-lung
#14
REVIEW
Mark Kuehnel, Lavinia Maegel, Jens Vogel-Claussen, Jan Lukas Robertus, Danny Jonigk
Following lung transplantation, fibrotic remodelling of the small airways has been recognized for almost 5 decades as the main correlate of chronic graft failure and a major obstacle to long-term survival. Mainly due to airway fibrosis, pulmonary allografts currently show the highest attrition rate of all solid organ transplants, with a 5-year survival rate of 58 % on a worldwide scale. The observation that these morphological changes are not just the hallmark of chronic rejection but rather represent a manifestation of a multitude of alloimmune-dependent and -independent injuries was made more recently, as was the discovery that chronic lung allograft dysfunction manifests in different clinical phenotypes of respiratory impairment and corresponding morphological subentities...
November 12, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27834175/severe-asthma-anti-ige-or-anti-il-5
#15
REVIEW
Evgenia Papathanassiou, Stelios Loukides, Petros Bakakos
Severe asthma is a discrete clinical entity characterised by recurrent exacerbations, reduced quality of life and poor asthma control as ordinary treatment regimens remain inadequate. Difficulty in managing severe asthma derives partly from the multiple existing phenotypes and our inability to recognise them. Though the exact pathogenetic pathway of severe allergic asthma remains unclear, it is known that numerous inflammatory cells and cytokines are involved, and eosinophils represent a key inflammatory cell mediator...
2016: European Clinical Respiratory Journal
https://www.readbyqxmd.com/read/27829417/administration-of-jte013-abrogates-experimental-asthma-by-regulating-proinflammatory-cytokine-production-from-bronchial-epithelial-cells
#16
Tomomi Terashita, Kazuyuki Kobayashi, Tatsuya Nagano, Yoshitaka Kawa, Daisuke Tamura, Kyosuke Nakata, Masatsugu Yamamoto, Motoko Tachihara, Hiroshi Kamiryo, Yoshihiro Nishimura
BACKGROUND: Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that acts as a signal transducer by binding to S1P receptors (S1PR) 1 to 5. The S1P/S1PRs pathway has been associated with remodeling and allergic inflammation in asthma, but the expression pattern of S1PR and its effects on non-immune cells have not been completely clarified. The aim of this study was to examine the contribution of the signaling of S1P and S1PRs expressed in airway epithelial cells (ECs) to asthma responses in mice...
November 9, 2016: Respiratory Research
https://www.readbyqxmd.com/read/27826959/inhibitory-effects-of-resveratrol-on-airway-remodeling-by-transforming-growth-factor-%C3%AE-smad-signaling-pathway-in-chronic-asthma-model
#17
Hwa Young Lee, In Kyoung Kim, Hyoung Kyu Yoon, Soon Suk Kwon, Chin Kook Rhee, Sook Young Lee
PURPOSE: Asthma is a chronic airway disease characterized by airway remodeling, leading to a progressive decline in lung function. Therapeutic agents that attenuate airway remodeling can complement the limited effects of traditional glucocorticoids. In this study, we investigated the effect of resveratrol on allergic airway inflammation and remodeling in a murine model of chronic bronchial asthma. METHODS: Peribronchial smooth muscle thickening that developed in mice challenged with a 3-month repeated exposure to ovalbumin (OVA) was used to study airway remodeling...
January 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/27817787/-effect-of-montelukast-sodium-intervention-on-airway-remodeling-and-percentage-of-th17-cells-cd4-cd25-regulatory-t-cells-in-asthmatic-mice
#18
Li Li, Chun-Yan Lou, Min Li, Jian-Bo Zhang, Jie Chen
OBJECTIVE: To study the dynamic changes in the percentage of Th17 cells/CD4(+)CD25(+) regulatory T cells after intervention with montelukast sodium, a leukotriene receptor antagonist, in asthmatic mice and the association between them. METHODS: Balb/c mice were randomly divided into blank group, asthma group, and montelukast sodium group. The asthmatic mouse model of airway remodeling was established by sensitization with intraperitoneal injection of chicken ovalbumin (OVA) and aluminum hydroxide suspension and aerosol inhalation of OVA...
November 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/27812543/duox1-mediates-persistent-epithelial-egfr-activation-mucous-cell-metaplasia-and-airway-remodeling-during-allergic-asthma
#19
Aida Habibovic, Milena Hristova, David E Heppner, Karamatullah Danyal, Jennifer L Ather, Yvonne M W Janssen-Heininger, Charles G Irvin, Matthew E Poynter, Lennart K Lundblad, Anne E Dixon, Miklos Geiszt, Albert van der Vliet
Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite-induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1)...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27807867/increase-of-poorly-proliferated-p63-ki67-basal-cells-forming-multiple-layers-in-the-aberrant-remodeled-epithelium-in-nasal-polyps
#20
Li Zhao, Ying Ying Li, Chun Wei Li, Siew Shuen Chao, Jing Liu, Ha Nguyen Nam, Dung Nguyen Thi Ngoc, Li Shi, De Yun Wang
BACKGROUND: Aberrant epithelial remodeling with the ectopic expression of p63 (basal cell markers) is an important pathologic phenomenon seen in chronically inflamed airway epithelium such as in nasal polyps (NPs). METHODS: Biopsies were obtained from 55 NP patients and 18 healthy controls (inferior turbinate). Among NP patients, fifteen were treated with oral and nasal steroids, so that two sets of NPs biopsies were taken before and after the treatments. p63, Ki67, type IV β-tubulin and cell-cycle markers were investigated in these specimens...
November 2, 2016: Allergy
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