Abstract:
BACKGROUND:Work-place exposure to silica dust may lead to progressive lung inflammation culminating in the development of silicosis, an irreversible condition that can be complicated by onset of pulmonary hypertension (PH). The molecular mechanisms leading to the development of PH and lung fibrosis in response to silica are not well understood. Oxidant/antioxidant imbalance in the lung may promote fibroproliferation and vascular smooth muscle proliferation, ultimately leading to the development of PH. Herein, we analyze the development of PH and lung fibrosis in mice deficient in extracellular superoxide dismutase (SOD3), an enzyme with anti-oxidant activity. METHODS:PH and silicosis were induced in wild-type and Sod3-/- mice through intratracheal injection of crystalline silica at dose 0.4 g/kg. Pulmonary hypertension and lung fibrosis were characterized by changes in right ventricular systolic pressure (RVSP) and collagen deposition 28 days following silica injections. Vascular remodeling was analyzed using immunohistochemistry and morphometric analysis. The expression of genes were analyzed using qRT-PCR and Western blot. RESULTS:C57BL6 mice exposed to silica showed attenuated expression of Sod3 in the lung suggesting a protective role for Sod3. Consistent with this, Sod3-/- mice developed more severe fibrotic inflammatory nodules with increased collagen deposition. Furthermore, the expression of genes involved in tissue remodeling (Timp1), fibrotic lesion formation (Fsp1) and inflammatory response (Mcp1) were significantly elevated in Sod3-/- mice compared to Sod3+/+ mice treated with silica. Infiltration of neutrophils and activated macrophages into affected lung was significantly higher in Sod3 deficient mice. In addition, silica produced more profound effects on elevation of RVSP in Sod3-/- compared to wild-type littermate. Increase in RVSP was concomitant with hypertrophy of pulmonary arteries located in silicotic nodules of both mouse strains, however, vascular remodeling in unaffected areas of lung was detected only in Sod3-/- mice. CONCLUSIONS:Our data suggest that Sod3 and extracellular oxidative stress may play an important role in the development of pneumoconiosis and pulmonary vascular remodeling following exposure to environmental and occupational silica.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Zelko IN,Zhu J,Roman Jdoi
10.1186/s12931-018-0933-6subject
Has Abstractpub_date
2018-11-20 00:00:00pages
221issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-018-0933-6journal_volume
19pub_type
杂志文章abstract:RATIONALE:Smoking-induced chronic obstructive pulmonary disease (COPD) is associated with acquired systemic cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Recently, sweat evaporimetry has been shown to efficiently measure β-adrenergic sweat rate and specifically quantify CFTR function in the se...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-15-25
更新日期:2014-02-25 00:00:00
abstract:BACKGROUND:Exhaled nitric oxide (F(E)NO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F(E)NO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F(E)NO in ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-82
更新日期:2007-11-15 00:00:00
abstract:BACKGROUND:Pulmonary arterial hypertension (PAH) is associated with inflammatory response but it is unknown whether it is associated with alterations in NNMT activity and MNA plasma concentration. Here we examined changes in NNMT-MNA pathway in PAH in rats and humans. METHODS:PAH in rats was induced by a single subcut...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0423-7
更新日期:2016-08-31 00:00:00
abstract:BACKGROUND:Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01513-x
更新日期:2020-10-13 00:00:00
abstract:BACKGROUND:Myofibroblasts, proposed as being derived from circulating fibrocytes, are considered to be important cells in thickening of the basement membrane in patients with asthma. We have studied the correlation of tissue fibrocyte levels to basement membrane thickness and the presence of fibrocytes in bronchoalveol...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-50
更新日期:2006-03-29 00:00:00
abstract:BACKGROUND:During 2007-2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6-79 years and post-bronchodilator pulmonary lung function data for the subse...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-14-103
更新日期:2013-10-09 00:00:00
abstract:BACKGROUND:Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) a...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0452-2
更新日期:2016-10-27 00:00:00
abstract:BACKGROUND:ATP-regulated potassium channels (KATP) regulate pulmonary vascular tone and are involved in hypoxic pulmonary vasoconstriction (HPV). In patients with inflammation like sepsis or ARDS, HPV is impaired, resulting in a ventilation-perfusion mismatch and hypoxia. Since increase of vascular KATP channel Kir6.1 ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0735-x
更新日期:2018-02-13 00:00:00
abstract:BACKGROUND:Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure. METHODS:Mice were exposed to cigare...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-81
更新日期:2012-09-19 00:00:00
abstract:BACKGROUND:The development of bronchial hyperreactivity (BHR) subsequent to precapillary pulmonary hypertension (PHT) was prevented by acting on the major signalling pathways (endothelin, nitric oxide, vasoactive intestine peptide (VIP) and prostacyclin) involved in the control of the pulmonary vascular and bronchial t...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-58
更新日期:2011-04-27 00:00:00
abstract:BACKGROUND:Real-world evidence (RWE) can inform patient management decisions, but RWE studies are associated with limitations. Linkage of different RWE data types could address such limitations by enriching data and improving scientific quality. Using the example of chronic obstructive pulmonary disease (COPD) in Germa...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0865-1
更新日期:2018-08-30 00:00:00
abstract:BACKGROUND:The burden of symptoms and risk of exacerbations are the main drivers of the overall assessment of the Chronic Obstructive Pulmonary Disease (COPD) and the adequate treatment approaches per current Global Initiative for Chronic Obstructive Lung Disease (GOLD). Physical activity has emerged as both functional...
journal_title:Respiratory research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/s12931-019-1053-7
更新日期:2019-05-14 00:00:00
abstract:BACKGROUND:Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjec...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-52
更新日期:2008-07-11 00:00:00
abstract:BACKGROUND:Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investig...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-103
更新日期:2012-11-17 00:00:00
abstract:: ...
journal_title:Respiratory research
pub_type: 社论
doi:10.1186/s12931-018-0929-2
更新日期:2018-11-26 00:00:00
abstract:BACKGROUND:Recent studies have indicated the presence of multipotent mesenchymal stromal cells (MSCs) in human lung diseases. Excess airway smooth muscle, myofibroblasts and activated fibroblasts have each been noted in asthma, suggesting that mesenchymal progenitor cells play a role in asthma pathogenesis. We therefor...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-127
更新日期:2010-09-21 00:00:00
abstract:BACKGROUND:Sarcoidosis is an idiopathic granulomatous disease with pathologic and immunologic features similar to tuberculosis. Routine histologic staining and culture fail to identify infectious agents. An alternative means for investigating a role of infectious agents in human pathogenesis involves molecular analysis...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-36
更新日期:2008-04-25 00:00:00
abstract:BACKGROUND:Adolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of tr...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0153-7
更新日期:2014-11-29 00:00:00
abstract:BACKGROUND:Stress of the endoplasmic reticulum (ER) leading to activation of the unfolded protein response (UPR) and alveolar epithelial cell (AEC) apoptosis may play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our objectives were to determine whether circulating caspase-cleaved cytokeratin-18 (c...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-105
更新日期:2012-11-20 00:00:00
abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation and impaired immune response to pathogens leading to bacteria-induced exacerbation of the disease. A defect in Th17 cytokines in response to Streptococcus pneumoniae, a bacteria associated with COPD exacerbations, has been r...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0408-6
更新日期:2016-07-26 00:00:00
abstract:BACKGROUND:The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with "sharp" large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM p...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-017-0551-8
更新日期:2017-04-20 00:00:00
abstract:BACKGROUND:A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known. METHODS:ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavag...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01446-5
更新日期:2020-07-16 00:00:00
abstract:BACKGROUND:The discrepancy between functional and inflammatory airway response to ozone has been reported in normal subjects, but few data are available for stable asthmatics regularly treated with inhaled corticosteroids. METHODS:Twenty-three well controlled, regularly treated, mild-to-moderate asthmatic patients und...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-11-5
更新日期:2010-01-19 00:00:00
abstract:BACKGROUND:Family history of asthma and other allergic diseases have been linked to the risk of childhood asthma previously, but little is known about their effect on the age-of-onset and persistency of asthma until young adulthood. METHODS:We assessed the effect of the family history of asthma and allergic diseases o...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0152-8
更新日期:2014-11-27 00:00:00
abstract:BACKGROUND:The relative contributions of the cytotoxic phenotype of P. aeruginosa expressing type III secretory toxins and an immunocompromised condition lacking normal Toll-like receptor 4 (TLR4) signaling in the pathogenesis of acute lung injury and sepsis were evaluated in a mouse model for Pseudomonas aeruginosa pn...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-5-1
更新日期:2004-02-12 00:00:00
abstract:OBJECTIVES:Swimming is one of the most popular forms of physical activity. Pool water is cleaned with chlorine, which - in combination with compounds contained in water - could form chloramines and trichloromethane in the swimmer's lungs. The aim of the present study was to examine the effect of swimming training in an...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01350-y
更新日期:2020-04-15 00:00:00
abstract:OBJECTIVE:To investigate the differences in the proportions of BMPR2 mutations in familial hereditary pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH) between males and females and the relationship between BMPR2 mutation and PAH severity. METHODS:A computer was used to searc...
journal_title:Respiratory research
pub_type: 杂志文章,meta分析
doi:10.1186/s12931-020-1309-2
更新日期:2020-02-06 00:00:00
abstract:BACKGROUND:Possible variation in bronchodilator response (BDR) according to age at the diagnosis of adult-onset asthma is unknown. Our aim was to assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR, the suggested cut-off for asthma-like re...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01441-w
更新日期:2020-07-13 00:00:00
abstract:BACKGROUND:The human small airway epithelium (SAE) plays a central role in the early events in the pathogenesis of most inherited and acquired lung disorders. Little is known about the molecular phenotypes of the specific cell populations comprising the SAE in humans, and the contribution of SAE specific cell populatio...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01442-9
更新日期:2020-07-29 00:00:00
abstract::The role of autoimmunity targeting epithelial antigens in asthma has been suggested, in particular in non-atopic and severe asthma. Periplakin, a desmosomal component, is involved in epithelial cohesion and intracellular signaling. We detected anti-periplakin IgG antibodies in 47/260 (18 %) patients with asthma, with ...
journal_title:Respiratory research
pub_type: 信件
doi:10.1186/s12931-016-0441-5
更新日期:2016-10-07 00:00:00