Abstract:
:While signal transducer and activator of transcription protein 6 (STAT6) is important in interleukin-4 (IL-4)-induced commitment of CD4(+) T cells to the T helper cell, type 2 (Th2) phenotype and IgE isotype switching in B cells, its role in other IL-4-mediated events and their impact upon the allergic response is less evident. In the present study we demonstrate the critical role of STAT6 in the development of allergic airway eosinophilia and airway hyperresponsiveness (AHR) after allergen sensitization and challenge. STAT6-deficient (STAT6-/-) mice did not develop a Th2 cytokine response or an allergen-specific IgE response. Further, STAT6-/- mice had a reduced constitutive and allergen-induced expression of CD23 as well as lower mucus production in the airway epithelium. Critically, we show that IL-5 alone can reconstitute airway eosinophilia and AHR in sensitized and challenged STAT6-/- mice. This emphasizes the essential nature of the IL-4-dependent signaling of T cells to the Th2 phenotype and secretion of IL-5, resulting in the airway eosinophilia and AHR. These observations underscore the importance of targeting this pathway in new antiallergic asthma drug development.
journal_name
Am J Respir Crit Care Medauthors
Tomkinson A,Kanehiro A,Rabinovitch N,Joetham A,Cieslewicz G,Gelfand EWdoi
10.1164/ajrccm.160.4.9809065keywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
1283-91issue
4eissn
1073-449Xissn
1535-4970journal_volume
160pub_type
杂志文章abstract:RATIONALE:Idiopathic pulmonary fibrosis (IPF) is caused by alterations in expression of proteins involved in multiple pathways, including matrix deposition, inflammation, injury, and repair. OBJECTIVES:To understand the pathogenic changes in lung protein expression in IPF and to evaluate apolipoprotein (Apo) A-I as a ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200905-0659OC
更新日期:2010-09-01 00:00:00
abstract:RATIONALE:IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. OBJECTIVES:The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier st...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200909-1462OC
更新日期:2011-04-01 00:00:00
abstract:RATIONALE:Occupational exposure to beryllium (Be) can result in chronic granulomatous inflammation characterized by the presence of Be-specific CD4+ T cells. Studies show that oxidative stress plays a role in the pathogenesis of chronic inflammatory disorders. OBJECTIVES:We hypothesized that Be-induced oxidative stres...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200707-1021OC
更新日期:2008-05-01 00:00:00
abstract::Increased serum levels of mucin-associated antigen have been previously demonstrated in patients with cystic fibrosis (CF) and interstitial pneumonia, and in lung-transplant recipients. The present study assessed the serum airway mucin levels in patients with acute respiratory distress syndrome (ARDS). An enzyme-linke...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.5.9701061
更新日期:1997-11-01 00:00:00
abstract::Previous studies suggest that lung function tests using monodisperse aerosols can help to identify early stages of lung diseases. We investigated intrapulmonary particle loss and aerosol bolus dispersion-a marker of convective gas transport-in 32 women with asymptomatic nonspecific bronchial hyperresponsiveness (BHR) ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.3.9805036
更新日期:1999-03-01 00:00:00
abstract:RATIONALE:The effect of indoor air pollutants on respiratory morbidity among patients with chronic obstructive pulmonary disease (COPD) in developed countries is uncertain. OBJECTIVES:The first longitudinal study to investigate the independent effects of indoor particulate matter (PM) and nitrogen dioxide (NO(2)) conc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201211-1987OC
更新日期:2013-05-15 00:00:00
abstract::An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disod...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.156.5.9611088
更新日期:1997-11-01 00:00:00
abstract:RATIONALE:Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in asthma pathogenesis, but it remains unknown how their phenotype, location, and activation relate to asthma severity. OBJECTIVES:To compare MC-related markers measured in bronchoscopically obtained samples with clinically relevant...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201002-0295OC
更新日期:2011-02-01 00:00:00
abstract::Secretory leukocyte protease inhibitor (SLPI) and elafin are structurally similar, low-molecular-weight antiproteases produced in the lung. We have developed a simple method for distinguishing the antiprotease activities of SLPI and elafin in lung lavage fluid from those of alpha 1-antitrypsin (alpha 1-AT) that is bas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.152.5.7582300
更新日期:1995-11-01 00:00:00
abstract::A group of male amateur cyclists was studied in the summer of 1991 in the east of the Netherlands. Lung function was measured before and after training sessions or competitive races on a number of occasions. Continuous heart rate monitors were employed to document exercise levels. Heart rate averaged 161 beats/min dur...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.4.7921470
更新日期:1994-10-01 00:00:00
abstract::Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinar...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.153.2.8564100
更新日期:1996-02-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201802-0375OC
更新日期:2019-06-01 00:00:00
abstract::The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS)....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.1.8542150
更新日期:1996-01-01 00:00:00
abstract::Studies of the hemodynamic effects of nasal continuous positive airway pressure (n-CPAP) in normal subjects have had conflicting results. The largest study (n = 19) found no effect of up to 15 cm H2O on heart rate (HR), cardiac stroke volume (SV), or cardiac index. We hypothesized that n-CPAP, by increasing intrathora...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.149.6.8004320
更新日期:1994-06-01 00:00:00
abstract:RATIONALE:Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. OBJECTIVES:To identify patient char...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.201503-0450OC
更新日期:2015-06-15 00:00:00
abstract:RATIONALE:Defective efferocytosis (phagocytic clearance of apoptotic cells) in the airway may perpetuate inflammation via secondary necrosis in chronic obstructive pulmonary disease (COPD). We have previously reported that low-dose azithromycin improved alveolar macrophage (AM) phagocytic function in vitro. OBJECTIVES...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200711-1666OC
更新日期:2008-07-15 00:00:00
abstract::Although impairment of gas exchange caused by ventilation-perfusion (VA/Q) mismatch has been extensively analyzed, there have been no systematic studies focused on determining the distributions of diffusion properties in dose connection with those of VA/Q. We attempted to clarify the simultaneous distributions of VA/Q...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.1.9607090
更新日期:1997-07-01 00:00:00
abstract:RATIONALE:The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200504-525OC
更新日期:2005-11-15 00:00:00
abstract:RATIONALE:Cigarette smoking is a risk factor for diffuse parenchymal lung disease. Risk factors for subclinical parenchymal lung disease have not been described. OBJECTIVES:To determine if cigarette smoking is associated with subclinical parenchymal lung disease, as measured by spirometric restriction and regions of h...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200812-1966OC
更新日期:2009-09-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.1.9712061
更新日期:1998-07-01 00:00:00
abstract:RATIONALE:Severe pulmonary arterial hypertension (PAH) is characterized by the formation of plexiform lesions and concentric intimal fibrosis in small pulmonary arteries. The origin of cells contributing to these vascular lesions is uncertain. Endogenous endothelial progenitor cells are potential contributors to this p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200810-1662OC
更新日期:2009-10-15 00:00:00
abstract::Inhaled corticosteroids are effective antiinflammatory therapy for asthma; however, they do not completely abolish allergen-induced airway inflammation. Leukotriene modifiers attenuate both early and late allergen responses and have antiinflammatory properties. We reasoned that treatment with budesonide and montelukas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/rccm.200206-509OC
更新日期:2002-11-01 00:00:00
abstract::Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, 68Ga-2-(p-...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201903-0639OC
更新日期:2020-01-01 00:00:00
abstract:RATIONALE:Endobronchial ultrasound (EBUS) and electromagnetic navigation bronchoscopy (ENB) have increased the diagnostic yield of bronchoscopic diagnosis of peripheral lung lesions. However, the role of combining these modalities to overcome each individual technique's limitations and, consequently, to further increas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.200612-1866OC
更新日期:2007-07-01 00:00:00
abstract::A noninvasive method to characterize inflammation and infection in the airways of nonexpectorating children with cystic fibrosis (CF) is needed for clinical and research purposes. Accordingly, we performed sputum inductions by administering 3% saline to 11 healthy control children and 20 children with CF, composed of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.8.2104075
更新日期:2001-10-15 00:00:00
abstract::At the time of diagnosis, many sarcoidosis patients have no clinical indication for corticosteroid therapy, and prognostic parameters predicting deterioration are missing. In the present study, we investigated parameters derived from bronchoalveolar lavage (BAL) and serum in 77 patients with recently diagnosed sarcoid...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.5.97-02050
更新日期:1997-11-01 00:00:00
abstract::The aim of this study was to assess positive end-expiratory pressure (PEEP)-induced lung overdistension and alveolar recruitment in six patients with acute lung injury (ALI) using a computed tomographic (CT) scan method. Lung overdistension was first determined in six healthy volunteers in whom CT sections were obtain...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.5.9802101
更新日期:1998-11-01 00:00:00
abstract:RATIONALE:Patients with obstructive sleep apnea (OSA) adapt to the anatomical vulnerability of their upper airway by generating increased activity in upper airway-dilating muscles during wakefulness. Norepinephrine (NE) and serotonin (5-HT) mediate, through α₁-adrenergic and 5-HT₂A receptors, a wake-related excitatory ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200912-1884OC
更新日期:2010-11-15 00:00:00
abstract::Quality of life has been found to be impaired both in patients with asthma and in patients with allergic rhinitis, but the relative burden of these diseases has not been investigated. We analyzed answers to the SF-36 questionnaire from 850 subjects recruited in two French centers participating in the European Communit...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.4.9912033
更新日期:2000-10-01 00:00:00
abstract:RATIONALE:A loss of function mutation in the cystic fibrosis transmembrane conductance regulator gene is believed to be an independent risk factor for bone disease in patients with cystic fibrosis. OBJECTIVES:The objective of this work was to use congenic mice as a preclinical model to examine the bone phenotype of Cf...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200705-659OC
更新日期:2008-02-01 00:00:00