Abstract:
RATIONALE:Despite intensive research, sepsis displays the most prevalent cause of death on intensive care units. The hallmark of sepsis is an overshooting T-cell death that reduces host defense mechanisms and that is associated with poor patient survival. Previous in vitro studies revealed that the expression of the transcription factor peroxisome proliferator-activated receptor (PPAR) γ was increased in isolated T cells of patients with sepsis. OBJECTIVES:We determined the importance of targeting PPARγ for sepsis treatment and underlying molecular mechanisms for T-cell apoptosis in vivo. METHODS:To mimic human systemic inflammation and septic conditions, we used a nonlethal endotoxemia and a lethal cecum ligation and puncture polymicrobial sepsis model. MEASUREMENTS AND MAIN RESULTS:PPARγ inhibition in T cells with either the PPARγ antagonist GW9662 or a newly generated T cell-specific PPARγ knockout (Tc-PPARγ(-/-)) mice provided a survival advantage during polymicrobial sepsis in mice, which correlated with abrogated T-cell depletion in both in vivo models. Pathway analysis revealed increased antiapoptotic IL-2 and Bcl-2 expression, and activated prosurvival PI3K/Akt signaling under PPARγ-deficient conditions. In line, neutralizing IL-2 in Tc-PPARγ(-/-) mice resulted in T-cell apoptosis and increased mortality. CONCLUSIONS:Our results provide evidence for a pivotal involvement of PPARγ in T-cell depletion by activating two important apoptosis pathways, and subsequently provoking the breakdown of defense mechanisms during systemic inflammation and sepsis.
journal_name
Am J Respir Crit Care Medauthors
Schmidt MV,Paulus P,Kuhn AM,Weigert A,Morbitzer V,Zacharowski K,Kempf VA,Brüne B,von Knethen Adoi
10.1164/rccm.201010-1585OCsubject
Has Abstractpub_date
2011-07-01 00:00:00pages
64-74issue
1eissn
1073-449Xissn
1535-4970pii
201010-1585OCjournal_volume
184pub_type
杂志文章abstract::Acute respiratory distress syndrome (ARDS) is characterized by an extensive alveolar capillary leak, permitting contact between intra-alveolar factors and the endothelium. To investigate whether factors contained in the alveolar milieu induce cell death in human lung microvascular endothelial cells, we exposed these c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2109004
更新日期:2002-09-01 00:00:00
abstract:RATIONALE:Transthoracic Doppler echocardiography is recommended for screening for the presence of pulmonary hypertension (PH). However, some recent studies have suggested that Doppler echocardiographic pulmonary artery pressure estimates may frequently be inaccurate. OBJECTIVES:Evaluate the accuracy of Doppler echocar...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200811-1691OC
更新日期:2009-04-01 00:00:00
abstract:RATIONALE:Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. OBJECTIVES:To evaluate the safety and efficacy of tezacaft...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.201704-0717OC
更新日期:2018-01-15 00:00:00
abstract::Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size (approximately 1 mm in diameter) bronchi. Here, we have investigated the presence and biological responses of NK1 receptors in medium-size (2-5 mm in diameter) human...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.5.2002079
更新日期:2001-04-01 00:00:00
abstract::Ethane is a product of lipid peroxidation as a result of oxidative stress and can be detected in the exhaled air. Oxidative stress plays a role in the pathogenesis of asthma. We measured exhaled ethane in 26 asthmatic subjects (mean age +/- SEM, 38 +/- 8 yr; 15 male, FEV(1) 60 +/- 4%) and compared it with exhaled nitr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.4.2003064
更新日期:2000-10-01 00:00:00
abstract:RATIONALE:Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. OBJECTIVES:Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidativ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.201801-0105OC
更新日期:2018-09-01 00:00:00
abstract::Airway inflammation is involved in the pathogenesis of bronchial asthma. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 alpha (LFA-1 alpha) and has been shown to be required for leukocyte migration into inflamed area. The purpose of this report was to investigate th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/151.4.1244
更新日期:1995-04-01 00:00:00
abstract::Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Ev...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,实务指引
doi:10.1164/rccm.201908-1581ST
更新日期:2019-10-01 00:00:00
abstract::The role of nitric oxide (NO) in the host-defense against human tuberculosis (TB) is controversial. Although experimental evidence indicates that NO may play an important role in controlling TB, its expression in human tuberculous lungs has not been systematically characterized. We therefore investigated the expressio...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2201023
更新日期:2002-07-15 00:00:00
abstract::Allergen inhalation challenge is associated with increases in eosinophil number and activation, and provides a useful model for investigating airway inflammation in asthma. Limited information, however, is available on the effect of allergen challenge on cytokines regulating eosinophil function. We investigated allerg...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.6.7767540
更新日期:1995-06-01 00:00:00
abstract:RATIONALE:Intensive care unit (ICU) nurses work in a demanding environment where they are repetitively exposed to traumatic situations and stressful events. The psychological effects on nurses as a result of working in the ICU are relatively unknown. OBJECTIVE:To determine whether there is an increased prevalence of p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200606-735OC
更新日期:2007-04-01 00:00:00
abstract:RATIONALE:As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES:Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS:A total of 4,104 parti...
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.201505-1040OC
更新日期:2016-03-01 00:00:00
abstract:RATIONALE:The prevalence of vitamin D deficiency is increasing and has been linked to obstructive lung diseases including asthma and chronic obstructive pulmonary disease. Recent studies suggest that vitamin D deficiency is associated with reduced lung function. The relationship between vitamin D deficiency and lung fu...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201010-1596OC
更新日期:2011-05-15 00:00:00
abstract::We describe two reliable methods for high-throughput screening of proteinase inhibitor (PI) S and PI Z alpha(1)-antitrypsin (alpha(1)-AT) deficiency alleles from dried blood spot (DBS) specimens using the LightCycler fluorimetric analyzer. The method was used to study 72 patients with chronic obstructive pulmonary dis...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2203025
更新日期:2002-09-15 00:00:00
abstract:RATIONALE:The rate of progression of most interstitial lung diseases (ILD) is unpredictable. Fibrocytes are circulating bone marrow-derived cells that have been implicated in the pathogenesis of lung fibrosis. Hermansky-Pudlak syndrome (HPS), a genetic cause of ILD in early adulthood, allows for study of biomarkers of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201407-1287OC
更新日期:2014-12-15 00:00:00
abstract::We present a case of a pulmonary nodular lesion in an immunocompetent patient documented at open lung biopsy to be due to Mycobacterium haemophilum. This organism has recently been recognized as a cause of disease in immunocompromised patients, presenting predominantly as skin lesions, arthritis, and rarely pneumonia....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.160.4.9904003
更新日期:1999-10-01 00:00:00
abstract::The relationships between mite and cat allergen levels in the home, skin test reactivity, and severity of asthma were explored in 120 asthmatic subjects, 57 in Vancouver and 63 in Winnipeg. Patients in the two cities were similar in age, gender distribution, and severity of asthma. Skin tests were performed using 13 c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.6.8520740
更新日期:1995-12-01 00:00:00
abstract:RATIONALE:Standard physiologic assessments of extubation readiness in patients with acute hypoxemic respiratory failure (AHRF) may not reflect lung injury resolution and could adversely affect clinical decision-making and patient outcomes. OBJECTIVES:We hypothesized that elevations in inflammatory plasma biomarkers so...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.202005-1951OC
更新日期:2021-01-05 00:00:00
abstract:RATIONALE:Although intermittent, three-times-weekly therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium complex (MAC) lung disease, supporting data are limited. OBJECTIVES:To evaluate the clinical efficacy of intermittent therapy compared with daily therapy for no...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201408-1545OC
更新日期:2015-01-01 00:00:00
abstract:RATIONALE:Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in asthma. Its role in the disease process before the onset of respiratory symptoms remains unclear. OBJECTIVES:To examine whether elevated NO in newborns with clinically naive airways is associated with subsequent respirator...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200606-782OC
更新日期:2006-12-15 00:00:00
abstract::Interleukin-5 (IL-5) is a potent eosinophilopoietic factor implicated in the chronic inflammatory cell accumulation accompanying bronchial asthma. However, its role in stimulating eosinophil differentiation within the bone marrow following allergen exposure remains to be elucidated. The aims of our study were to deter...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.3.9709114
更新日期:1998-09-01 00:00:00
abstract::Pneumonectomized rats develop pulmonary hypertension (PH) and pulmonary vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/k...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.2.2006093
更新日期:2001-02-01 00:00:00
abstract::Fibrosing alveolitis may occur alone (CFA) or in association with systemic sclerosis (FASSc). FASSc was recently shown to have a prognostic advantage over CFA. Because interleukin-8 (IL-8) is likely to be a major determinant of neutrophil alveolitis, we evaluated IL-8 expression in patients with CFA and FASSc and comp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.5.7735620
更新日期:1995-05-01 00:00:00
abstract::Decision analysis was used to compare three alternative strategies for a 6-mo course of treatment for tuberculosis: directly observed drug therapy (DOT), self-administered fixed-dose combination drug therapy, and self-administered conventional individual drug therapy. Estimates of effectiveness were obtained from the ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.4.8887600
更新日期:1996-10-01 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::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 activated leukocyte cell adhesion molecule (ALCAM) is a cluster of differentiation 6 ligand that is important for stabilizing the immunological synapse and inducing T-cell activation and proliferation. OBJECTIVES:In this study, we investigated the role of ALCAM in the development of inflammation in aller...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201703-0532OC
更新日期:2018-04-15 00:00:00
abstract::Pulmonary tuberculosis, one of the granulomatous diseases, has few serological markers for its activity. Recently, an increased serum level of vascular endothelial growth factor (VEGF) was detected in patients with Crohn's disease, also a granulomatous disease. We hypothesized that VEGF might be associated with the pa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.3.9911010
更新日期:2000-09-01 00:00:00
abstract::Smoking is the major risk factor for chronic respiratory symptoms, but dietary factors may also play a role. Most studies of diet and lung disease have been cross-sectional and conducted in populations with a Western-style diet. We analyzed the relation between dietary intake at baseline and new onset of cough with ph...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200306-789OC
更新日期:2004-08-01 00:00:00
abstract::Physiologic adaptations after an 8-wk endurance training program were examined in 13 patients with chronic obstructive pulmonary disease (COPD) (age, 64 +/- 4 [SD] yr; FEV1, 43 +/- 9% pred; PaO2, 72 +/- 8 mm Hg; and PaCO2, 36 +/- 2 mm Hg) and in eight healthy sedentary control subjects (61 +/- 4 yr). Both pre- and pos...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9804136
更新日期:1999-06-01 00:00:00