Abstract:
:The lung epithelium constitutes a selective barrier that separates the airways from the aqueous interstitial compartment. Regulated barrier function controls water and ion transport across the epithelium and is essential for maintaining lung function. Tight junctions (TJs) seal the epithelial barrier and determine the paracellular transport. The properties of TJs depend especially on their claudin composition. Steroids are potent drugs used to treat a variety of airway diseases. Therefore, we addressed whether steroid hormones directly act on TJ properties in lung epithelia. Primary human tracheal epithelial cells and NCI-H441 cells, both cultivated under air-liquid interface conditions, were used as epithelial cell models. Our results demonstrate that glucocorticoids, but not mineralocorticoids, decreased paracellular permeability and shifted the ion permselectivity of TJs toward Cl(-). Glucocorticoids up-regulated claudin 8 (cldn8) expression via glucocorticoid receptors. Silencing experiments revealed that cldn8 is necessary to recruit occludin at the TJs. Immunohistochemistry on human lung tissue showed that cldn8 is specifically expressed in resorptive epithelia of the conducting and respiratory airways but not in the alveolar epithelium. We conclude that glucocorticoids enhance lung epithelia barrier function and increase paracellular Cl(-) selectivity via modulation of cldn8-dependent recruitment of occludin at the TJs. This mode of glucocorticoid action on lung epithelia might be beneficial to patients who suffer from impaired lung barrier function in various diseased conditions.
journal_name
Am J Respir Cell Mol Biolauthors
Kielgast F,Schmidt H,Braubach P,Winkelmann VE,Thompson KE,Frick M,Dietl P,Wittekindt OHdoi
10.1165/rcmb.2015-0071OCsubject
Has Abstractpub_date
2016-05-01 00:00:00pages
707-17issue
5eissn
1044-1549issn
1535-4989journal_volume
54pub_type
杂志文章abstract::Hyperplasia and cell migration of smooth muscle are features of both airway and pulmonary vascular diseases. The precise cellular and molecular mechanisms that regulate smooth muscle migration in the lungs remain unknown. In this study, we examined the effect of cAMP-mobilizing agents and steroids on smooth muscle cel...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0254OC
更新日期:2003-07-01 00:00:00
abstract::Pulmonary lymphangioleiomyomatosis (LAM), a disease of young women, is characterized by proliferation of immature-appearing smooth-muscle cells (LAM cells) in the lungs and abdomen. LAM cells react with monoclonal antibody HMB45, which recognizes a 100-kD glycoprotein (gp100) originally found in human melanoma cells. ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.21.3.3693
更新日期:1999-09-01 00:00:00
abstract::High mobility group box 1 (HMGB1) is an alarmin released from macrophages after infection or inflammation and is a biomarker of lung disease progression in patients with cystic fibrosis. We reported that 2-O, 3-O desulfated heparin (ODSH) inhibits the release of HMGB1 from murine macrophages triggered by neutrophil el...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0069OC
更新日期:2017-01-01 00:00:00
abstract::Asthma is characterized by appearance of eosinophils in the airway. Eosinophils purified from the airway 48 h after segmental antigen challenge are described as exhibiting greater adhesion to albumin-coated surfaces via an unidentified beta2 integrin and increased expression of alphaMbeta2 (CD11b/18) compared with pur...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0027OC
更新日期:2006-09-01 00:00:00
abstract::Infections with bacteria and viruses such as adenovirus are a feature of chronic lung diseases such as chronic obstructive pulmonary diseases (COPD), and may be instrumental in the generation of disease exacerbations. We have previously shown in acute models that elafin (a lung natural chemotactic molecule for macroph...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0405OC
更新日期:2006-05-01 00:00:00
abstract::Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among single-nucleotide polymorphisms (SNPs) in genes of the histamine ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2014-0493OC
更新日期:2015-12-01 00:00:00
abstract::Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease of preterm infants. The development of pulmonary hypertension (PH) significantly increases the mortality and morbidity of this disease. β-Catenin signaling plays an important role in tissue development and remodeling. Aberrant β-caten...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0346OC
更新日期:2014-07-01 00:00:00
abstract::The doxycycline-inducible, gene regulatory system allows tight control of transgene expression for the study of organ development and disease pathogenesis. Multiple recent reports have employed this model to investigate various lung diseases including emphysema. For our study, we used this transgenic system to test wh...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0378OC
更新日期:2006-05-01 00:00:00
abstract::Macrophages are the primary lung phagocyte and are instrumental in maintenance of a sterile, noninflamed microenvironment. IFNs are produced in response to bacterial and viral infection, and activate the macrophage to efficiently counteract and remove pathogenic invaders. Respiratory syncytial virus (RSV) inhibits IFN...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0229OC
更新日期:2010-04-01 00:00:00
abstract::Morphologic changes are reported to occur in rat lung vasculature after 3 days of hypoxia. We have previously shown that immunoreactivity for the vasodilator calcitonin gene-related peptide (CGRP) is increased in pulmonary endocrine cells by 7 days of hypoxia. Because these cells may be among the earliest mediators of...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/9.5.467
更新日期:1993-11-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is characterized by excessive deposition of extracellular matrix, in particular, collagens. Two IPF therapeutics, nintedanib and pirfenidone, decelerate lung function decline, but their underlying mechanisms of action are poorly understood. In this study, we sought to analyze their ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0217OC
更新日期:2017-07-01 00:00:00
abstract::Glucocorticoids increase surfactant phosphatidylcholine synthesis, in part, by stimulating the rate regulatory enzyme CTP:cholinephosphate cytidylyltransferase. This enzyme exists in mammalian lung cytosol as an active lipoprotein form (H-form) and an inactive apoprotein (L-form) species. We administered betamethasone...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.10.1.8292380
更新日期:1994-01-01 00:00:00
abstract::Inhalation of the pulmonary irritant ozone is associated with an accumulation of macrophages in the lung. These cells, along with type II epithelial cells, are activated to release increased quantities of hydrogen peroxide and nitric oxide, two reactive mediators that have been implicated in tissue injury. In the pres...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.14.6.8652180
更新日期:1996-06-01 00:00:00
abstract::Skeletal muscle atrophy in individuals with advanced chronic obstructive pulmonary disease (COPD) is associated with diminished quality of life, increased health resource use, and worsened survival. Muscle wasting results from an imbalance between protein degradation and synthesis, and is enhanced by decreased regener...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0382OC
更新日期:2010-04-01 00:00:00
abstract::We have determined eicosanoid production from endogenous arachidonic acid by neonatal lamb lungs stimulated with calcium ionophore A23187 during normoxia and hypoxia. Lungs of lambs 19 to 25 d of age were isolated and perfused with cell-free Krebs' bicarbonate buffer at a flow rate of 15 to 20 ml/kg/min. After 30 min ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/4.4.379
更新日期:1991-04-01 00:00:00
abstract::The extracellular matrix in asthmatic lungs contains abundant low-molecular-weight hyaluronan, and this is known to promote antigen presentation and allergic responses. Conversely, high-molecular-weight hyaluronan (HMW-HA), typical of uninflamed tissues, is known to suppress inflammation. We investigated whether HMW-H...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0111OC
更新日期:2017-01-01 00:00:00
abstract::We compared the chemical composition of salivary mucin glycopeptides from cystic fibrosis (CF) and from non-CF subjects and the adhesion of Pseudomonas aeruginosa to these different salivary glycopeptides. Three pools of CF saliva, four pools of non-CF saliva, one individual CF saliva, and one individual non-CF saliva...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/9.3.323
更新日期:1993-09-01 00:00:00
abstract::Fetal airway smooth muscle contracts to neural stimulation from early gestation. This study aimed to document the development of the nerves and ganglia within the bronchial tree of the fetal pig lung as the structural correlates for this function. The formation of these structures during lung development (pseudoglandu...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.21.5.3721
更新日期:1999-11-01 00:00:00
abstract::Neutrophil elastase (NE) is a major inflammatory mediator in cystic fibrosis (CF) that is a robust predictor of lung disease progression. NE directly causes airway injury via protease activity, and propagates persistent neutrophilic inflammation by up-regulation of neutrophil chemokine expression. Despite its key role...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0338RC
更新日期:2014-04-01 00:00:00
abstract::The role of pro-inflammatory cytokines in an animal model of allergic lung disease was examined by use of an interleukin-1 receptor antagonist (IL-1ra) and a specific bioassay for tumor necrosis factor (TNF). Ovalbumin-sensitized guinea pigs exhibit a marked bronchial hyperreactivity (assessed by airway responsiveness...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/8.4.365
更新日期:1993-04-01 00:00:00
abstract::Histamine was one of the first inflammatory mediators thought to be important in the pathophysiology of asthma, but it is not now thought to be a mediator with primary importance in airway constriction. However, histamine has several effects that may be relevant. One of these effects, its immunoregulatory role, has be...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.14.6.8652190
更新日期:1996-06-01 00:00:00
abstract::Increased airway responsiveness is linked to lung function decline and mortality in subjects with chronic obstructive pulmonary disease (COPD); however, the genetic contribution to airway responsiveness remains largely unknown. A genome-wide association study (GWAS) was performed using the Illumina (San Diego, CA) Hum...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,meta分析
doi:10.1165/rcmb.2014-0198OC
更新日期:2015-08-01 00:00:00
abstract::Inflammatory lung disease is associated with increased epithelial permeability, but it is unclear how inflammatory cells alter epithelial permeability. Neutrophils have azurophilic granules containing elastase, cathepsin G, and defensins which are released at sites of inflammation. Experiments using whole animals and ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.13.6.7576710
更新日期:1995-12-01 00:00:00
abstract::The ability of Pseudomonas aeruginosa to form antibiotic-resistant biofilms is thought to account for the inability of current therapies to resolve bacterial infections in the lungs of patients with cystic fibrosis (CF). We recently described a system in which highly antibiotic-resistant P. aeruginosa biofilms grow on...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0299OC
更新日期:2009-09-01 00:00:00
abstract::Cyclooxygenase-2 (COX-2) is a key enzyme involved in the inflammatory process that is rapidly induced in macrophages in response to LPS. Carbon monoxide (CO), a byproduct of heme oxygnease-1, can suppress proinflammatory response in various in vitro and in vivo models of inflammation. This study was undertaken to exam...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0154OC
更新日期:2006-08-01 00:00:00
abstract::Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are major causes of acute respiratory failure with high rates of morbidity and mortality. Although surfactant protein (SP)-D plays a critical role in pulmonary innate immunity and several clinical studies suggest that this protein...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2009-0436OC
更新日期:2011-05-01 00:00:00
abstract::The alveolar epithelium is a critical target for pulmonary viruses and can produce proinflammatory cytokines and chemokines upon viral infection. However, the molecular interactions between virus-infected alveolar epithelial cells and inflammatory cells, including polymorphonuclear leukocytes (PMNs), have not been tho...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2011-0230OC
更新日期:2012-06-01 00:00:00
abstract::We studied the relative roles of Duox2-derived reactive oxygen species (ROS) in host defense against influenza A virus (IAV) infection in normal human nasal epithelial cells and mouse nasal mucosa. We found that Duox2 primarily generated ROS rapidly after IAV infection in normal human nasal epithelial cells and that k...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2014-0334OC
更新日期:2015-10-01 00:00:00
abstract::Chemokine receptor (CCR) 5 is expressed on dendritic cells, macrophages, CD8 cells, memory CD4 T cells, and stromal cells, and is frequently used as a marker of T helper type 1 cells. Interventions that abrogate CCR5 or interfere with its ligand binding have been shown to alter T helper type 2-induced inflammatory res...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0465OC
更新日期:2011-12-01 00:00:00
abstract::Toll-interacting protein (TOLLIP) is an intracellular adaptor protein with diverse actions throughout the body. In a context- and cell type-specific manner, TOLLIP can function as an inhibitor of inflammation and endoplasmic reticulum stress, an activator of autophagy, or a critical regulator of intracellular vacuole ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2020-0470TR
更新日期:2020-11-24 00:00:00