Abstract:
RATIONALE:Mitochondria have important roles in intracellular energy generation, modulation of apoptosis, and redox-dependent intracellular signaling. Although reactive oxygen species (ROS) participate in the regulation of intracellular signaling pathways, including activation of nuclear factor (NF)-kappaB, there is only limited information concerning the role of mitochondrially derived ROS in modulating cellular activation and tissue injury associated with acute inflammatory processes. OBJECTIVES:To examine involvement of the mitochondrial electron transport chain complex I on LPS-mediated NF-kappaB activation in neutrophils and neutrophil-dependent acute lung injury. METHODS:Neutrophils incubated with rotenone or metformin were treated with bacterial lipopolysaccharide (LPS) to determine the effects of mitochondrial complex I inhibition on intracellular concentrations of reactive oxygen species, NF-kappaB activation, and proinflammatory cytokine expression. Acute lung injury was produced by intratracheal injection of LPS into control, metformin, or rotenone-treated mice. MEASUREMENTS AND MAIN RESULTS:Inhibition of complex I with either rotenone or the antihyperglycemic agent metformin was associated with increased intracellular levels of both superoxide and hydrogen peroxide, as well as inhibition of LPS-induced I kappaB-alpha degradation, NF-kappaB nuclear accumulation, and proinflammatory cytokine production. Treatment of LPS-exposed mice with rotenone or metformin resulted in inhibition of complex I in the lungs, as well as diminished severity of lung injury. CONCLUSIONS:These results demonstrate that mitochondrial complex I plays an important role in modulating Toll-like receptor 4-mediated neutrophil activation and suggest that metformin, as well as other agents that inhibit mitochondrial complex I, may be useful in the prevention or treatment of acute inflammatory processes in which activated neutrophils play a major role, such as acute lung injury.
journal_name
Am J Respir Crit Care Medauthors
Zmijewski JW,Lorne E,Zhao X,Tsuruta Y,Sha Y,Liu G,Siegal GP,Abraham Edoi
10.1164/rccm.200710-1602OCsubject
Has Abstractpub_date
2008-07-15 00:00:00pages
168-79issue
2eissn
1073-449Xissn
1535-4970pii
200710-1602OCjournal_volume
178pub_type
杂志文章abstract::Haemophilus influenzae and Streptococcus pneumoniae are common causes of respiratory tract infections. H. influenzae attach to receptor epitopes in mucins and in epithelial cell membranes. Attachment is followed by an epithelial cell cytokine response. Secreted cytokines then initiate inflammation, upset the integrity...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/154.4_Pt_2.S187
更新日期:1996-10-01 00:00:00
abstract:RATIONALE:In the absence of a surgical lung biopsy, patients diagnosed with idiopathic pulmonary fibrosis (IPF) in clinical practice could participate in the INPULSIS trials of nintedanib if they had honeycombing and/or traction bronchiectasis plus reticulation, without atypical features of usual interstitial pneumonia...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201602-0402OC
更新日期:2017-01-01 00:00:00
abstract:RATIONALE:The majority of previous studies investigating asthma genetics have focused on cohorts with stable disease and have not defined mechanisms important during acute asthma. CD14 and CC16 each play a key role in biologically important inflammatory pathways and the gene of each has a functional promoter-region pol...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200509-1367OC
更新日期:2006-03-15 00:00:00
abstract:RATIONALE:Respiratory syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking. Two major challenges have stalled antiviral development: ethical difficulties in performing pediatric proof-of-concept studies and the prevailing concept that the disease is immun...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201002-0221OC
更新日期:2010-11-15 00:00:00
abstract::Luteolin is a flavonoid that has been shown to reduce proinflammatory molecule expression in vitro. In the present study, we have tested the ability of luteolin to inhibit lipopolysaccharide (LPS)- induced lethal toxicity and proinflammatory molecule expression in vivo. Mice receiving LPS (Salmonella enteriditis LPS, ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.6.2101049
更新日期:2002-03-15 00:00:00
abstract::Cigarette smoking causes the development of chronic bronchitis and chronic obstructive pulmonary disease. We hypothesized that exposure to cigarette smoke might initiate release of inflammatory mediators by bronchial epithelial cells. To evaluate this, the effect of cigarette smoke extract (CSE) on IL-8 release from c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.5.9154890
更新日期:1997-05-01 00:00:00
abstract:RATIONALE:The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. OBJECTIVES:To determine the role of Rora in smoke-induced emphysema. METHODS:Cigarette smoke extract in vitro ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201111-2023OC
更新日期:2012-09-01 00:00:00
abstract:RATIONALE:Nasal polyps (NPs) are characterized by intense edema or formation of pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in their submucosa remain unclear. OBJECTIVES:We hypothesized that formation of a fibrin mesh retains plasma protei...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201207-1292OC
更新日期:2013-01-01 00:00:00
abstract::Rationale: Tidal expiratory flow limitation (tidal-EFL) is not completely avoidable by applying positive end-expiratory pressure and may cause respiratory and hemodynamic complications in ventilated patients with lungs prone to collapse. During spontaneous breathing, expiratory diaphragmatic contraction counteracts ti...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201909-1690OC
更新日期:2020-05-15 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::Systemic inflammation is present in chronic obstructive pulmonary disease (COPD), which has been linked to cardiovascular morbidity and mortality. We determined the effects of oral and inhaled corticosteroids on serum markers of inflammation in patients with stable COPD. We recruited 41 patients with mild to moderate ...
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.200404-543OC
更新日期:2004-10-01 00:00:00
abstract::Mechanical ventilation may promote overdistension-induced pulmonary lesions in patients with acute respiratory distress syndrome (ARDS). The static pressure-volume (P-V) curve of the respiratory system can be used to determine the lung volume and corresponding static airway pressure at which lung compliance begins to ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.1.7599810
更新日期:1995-07-01 00:00:00
abstract:RATIONALE:The CD40 protein plays important roles in cell-mediated and humoral immune responses, especially in immunoglobulin class-switching to IgE. OBJECTIVES:We tested the association of CD40 polymorphisms with the risk of asthma and the level of serum IgE and investigated the functional effect of associated polymor...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200609-1286OC
更新日期:2007-04-15 00:00:00
abstract::In order to assess the usefulness of sputum analysis in studying plasma-protein exudation and local secretion of proteins in the airways, we measured specific proteins in the sputum sol phase (SSP) and sputum gel phase (SGP) from patients with stable asthma or chronic obstructive pulmonary disease (COPD). Protein leve...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.6.7952610
更新日期:1994-12-01 00:00:00
abstract:RATIONALE:Roflumilast is a therapeutic agent in the treatment of chronic obstructive pulmonary disease (COPD). It has antiinflammatory effects; however, it is not known whether it can affect a biologic pathway implicated in COPD pathogenesis and progression. The self-propagating acetyl-proline-glycine-proline (AcPGP) p...
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.201503-0543OC
更新日期:2015-10-15 00:00:00
abstract::Pleural disease both before and after organ transplantation has important implications. Pleural effusions are common in candidates for heart, liver, and kidney transplantation. A thoracentesis is not mandatory in these patients, but it should be performed if clinical or radiologic features suggest that the effusion is...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.153.3.8630560
更新日期:1996-03-01 00:00:00
abstract::Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha released from alveolar macrophages (AM) in pulmonary tuberculosis (TB) are important in host defense against mycobacterial infection. Nitric oxide (NO) production is enhanced in AM of TB patients. We examined whether NO was implicated in (IL)-1beta and TNF-a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.1.9902113
更新日期:2000-01-01 00:00:00
abstract::The potent bronchoconstrictor and mitogenic actions of the peptide endothelin-1 (ET-1) on airway smooth muscle may contribute significantly to the bronchial obstruction observed in asthma. However, the status of the receptor-effector systems that mediate these actions of ET-1 in asthmatic airways is currently unknown....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.5.7582310
更新日期:1995-11-01 00:00:00
abstract::We investigated whether exposure to ozone (O(3)) 24 hours after an allergen challenge test would increase airway eosinophilia induced by allergen in subjects with mild asthma with late airway response. Twelve subjects with mild atopic asthma participated in a randomized, single-blind study. Subjects underwent allergen...
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.2201013
更新日期:2002-10-15 00:00:00
abstract::The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2112064
更新日期:2002-08-15 00:00:00
abstract::Daily symptom, peak expiratory flow rate (PEFR), and medication diaries are often used in clinical trials of treatments for asthma on the assumption that they provide a better estimate of clinical status than does a questionnaire completed in the clinic. We conducted a study with the aim of comparing the measurement p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.4.9912138
更新日期:2000-10-01 00:00:00
abstract::Bronchoalveolar lavage (BAL) is increasingly used in the pediatric age group. However, normal values for BAL fluid (BALF) constituents are lacking. As part of an investigation to define reference values in children, we studied lymphocyte surface markers of BALF in 28 children 3 to 16 yr of age without bronchopulmonary...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.1.7599820
更新日期:1995-07-01 00:00:00
abstract::Chronic beryllium disease (CBD) provides a model system in which to evaluate the antigen-stimulated, cell-mediated, immune response that leads to granulomatous lung disease. We hypothesized that beryllium salts would stimulate bronchoalveolar lavage (BAL) cell release of tumor necrosis factor-alpha (TNF-alpha) and lnt...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.6.9610040
更新日期:1997-12-01 00:00:00
abstract::Brush cells, also termed tuft, caveolated, multivesicular, and fibrillovesicular cells, are part of the epithelial layer in the gastrointestinal and respiratory tracts. The cells are characterized by the presence of a tuft of blunt, squat microvilli (approximately 120-140/cell) on the cell surface. The microvilli cont...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.200502-203WS
更新日期:2005-07-01 00:00:00
abstract:RATIONALE:Superoxide dismutase (SOD) 3 inhibits oxidative fragmentation of lung matrix components collagen I, hyaluronan, and heparan sulfate. Inherited change in SOD3 expression or function could affect lung matrix homeostasis and influence pulmonary function. OBJECTIVES:To identify novel SOD3 polymorphisms that are ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200804-549OC
更新日期:2008-11-01 00:00:00
abstract::The use of noninvasive methods of monitoring airway inflammation, such as exhaled nitric oxide (eNO) and induced sputum, has been shown to improve asthma monitoring and optimize treatment in adult patients with asthma. There is a lack of comparable data in children. Forty children with stable asthma eligible for inhal...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200409-1242OC
更新日期:2005-05-15 00:00:00
abstract::We evaluated positron emission tomographic imaging of pulmonary transgene expression, using an enhanced mutant herpes simplex virus-1 thymidine kinase as the reporter gene, in the lungs of normal rats. Sixteen rats were studied 3 days after an intratracheal administration of 5 x 10(9) to 1 x 10(11) viral particles of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200210-1217OC
更新日期:2003-05-01 00:00:00
abstract::In a prospective study, we screened specimens from 190 mechanically ventilated patients hospitalized in a surgical intensive care unit, and from the environment to assess risks and routes of colonization/infection. Specimens from various sites were collected on admission and once a week throughout each patient's stay....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.3.9702096
更新日期:1998-03-01 00:00:00
abstract::Lung transplantation with its attendant life-long immunosuppression contributes to bone loss and its sequelae, fractures and kyphosis, in patients with lung disease, many of whom already suffer from severe osteoporosis. Patients with cystic fibrosis (CF) are one of the most severely affected groups. We conducted a con...
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.162.3.2002051
更新日期:2000-09-01 00:00:00
abstract::In animal models of endotoxemia, sepsis is associated with the accumulation of leukocytes and altered microvascular perfusion. In order to test the hypothesis that bacterial sepsis upregulates leukocyte-endothelial adhesion, we used intravital microscopy to examine the flow behavior of leukocytes in the postcapillary ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.1.9609012
更新日期:1998-01-01 00:00:00