Abstract:
:Adenosine concentrations are elevated in the lungs of patients with asthma and chronic obstructive pulmonary disease, where it balances between tissue repair and excessive airway remodeling. We previously demonstrated that the activation of the adenosine A2A receptor promotes epithelial wound closure. However, the mechanism by which adenosine-mediated wound healing occurs after cigarette smoke exposure has not been investigated. The present study investigates whether cigarette smoke exposure alters adenosine-mediated reparative properties via its ability to induce a shift in the oxidant/antioxidant balance. Using an in vitro wounding model, bronchial epithelial cells were exposed to 5% cigarette smoke extract, were wounded, and were then stimulated with either 10 μM adenosine or the specific A2A receptor agonist, 5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA; 10 μM), and assessed for wound closure. In a subset of experiments, bronchial epithelial cells were infected with adenovirus vectors encoding human superoxide dismutase and/or catalase or control vector. In the presence of 5% smoke extract, significant delay was evident in both adenosine-mediated and CPCA-mediated wound closure. However, cells pretreated with N-acetylcysteine (NAC), a nonspecific antioxidant, reversed smoke extract-mediated inhibition. We found that cells overexpressing mitochondrial catalase repealed the smoke extract inhibition of CPCA-stimulated wound closure, whereas superoxide dismutase overexpression exerted no effect. Kinase experiments revealed that smoke extract significantly reduced the A2A-mediated activation of cyclic adenosine monophosphate-dependent protein kinase. However, pretreatment with NAC reversed this effect. In conclusion, our data suggest that cigarette smoke exposure impairs A2A-stimulated wound repair via a reactive oxygen species-dependent mechanism, thereby providing a better understanding of adenosine signaling that may direct the development of pharmacological tools for the treatment of chronic inflammatory lung disorders.
journal_name
Am J Respir Cell Mol Biolauthors
Allen-Gipson DS,Zimmerman MC,Zhang H,Castellanos G,O'Malley JK,Alvarez-Ramirez H,Kharbanda K,Sisson JH,Wyatt TAdoi
10.1165/rcmb.2011-0273OCsubject
Has Abstractpub_date
2013-05-01 00:00:00pages
665-73issue
5eissn
1044-1549issn
1535-4989pii
rcmb.2011-0273OCjournal_volume
48pub_type
杂志文章abstract::Glucocorticoid (GC) insensitivity represents a profound challenge in managing patients with asthma. The mutual inhibition of transcriptional activity between GC receptor (GR) and other regulators is one of the mechanisms contributing to GC resistance in asthma. We recently reported that interferon regulatory factor (I...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2009-0239RC
更新日期:2010-01-01 00:00:00
abstract::Cigarette smoking and aging are major risk factors for chronic obstructive pulmonary disease. An unsolved question is whether elderly lungs are particularly vulnerable to cigarette smoke (CS) exposure. In this study, we used a mouse model to test the hypothesis that aging increases the susceptibility to CS-induced pul...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2009-0025OC
更新日期:2010-03-01 00:00:00
abstract::Accumulating evidence has demonstrated that up-regulation of the angiotensin (Ang)-converting enzyme (ACE)/AngII/AngII type 1 receptor (AT1R) axis aggravates pulmonary fibrosis. The recently discovered ACE2/Ang-(1-7)/Mas axis, which counteracts the activity of the ACE/AngII/AT1R axis, has been shown to protect against...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0451OC
更新日期:2014-04-01 00:00:00
abstract::We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep) cells from normal (NN) and inflamed, allergic rhinitis (AR) and nasal polyp (NP) tissues to induce monocytic differentiation of hemopoietic progenitors of the HL-60 myeloid leukemia cell line in vitro. In HL-60 cells cul...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/4.3.255
更新日期:1991-03-01 00:00:00
abstract::Mechanical ventilation with supraphysiological concentrations of oxygen (hyperoxia) is routinely used to treat patients with respiratory distress. However, a significant number of patients on ventilators exhibit enhanced susceptibility to infections and develop ventilator-associated pneumonia (VAP). Pseudomonas aerugi...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0279OC
更新日期:2013-03-01 00:00:00
abstract::IL-11 and IL-11 receptor (R)alpha are induced by Th2 cytokines. However, the role(s) of endogenous IL-11 in antigen-induced Th2 inflammation has not been fully defined. We hypothesized that IL-11, signaling via IL-11Ralpha, plays an important role in aeroallergen-induced Th2 inflammation and mucus metaplasia. To test ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0053OC
更新日期:2008-12-01 00:00:00
abstract::Acute lung injury (ALI) is characterized by pulmonary inflammation and edema. Innate immune cells (e.g., neutrophils and macrophages) are major contributors to inflammation in ALI. Less is known regarding the role of T cells. We examined the effects of rapamycin on inflammation in a LPS-induced murine model of ALI. Ra...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0171OC
更新日期:2014-08-01 00:00:00
abstract::Increased activity of lung epithelial sodium channels (ENaCs) contributes to the pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial lining fluid reabsorption. Inter-α-inhibitor (IαI), a serum protease inhibitor, may decrease ENaC activity by preventing its cleavage by serine proteases. High c...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0215OC
更新日期:2014-05-01 00:00:00
abstract::The insulin-like growth factor (IGF)-II/mannose-6-phosphate (M6P) receptor, which targets acid hydrolases to lysosomes, is a multifunctional protein with separate binding sites for IGF-II and M6P. The purpose of this study was to determine if alveolar macrophages (AM) and their precursor cells, blood monocytes, expres...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/4.6.555
更新日期:1991-06-01 00:00:00
abstract::Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0489OC
更新日期:2015-06-01 00:00:00
abstract::Eotaxins-1, -2, and -3 mediate the recruitment of blood-borne eosinophils to allergically inflamed tissues by binding CC chemokine receptor (CCR) 3. Mast cells (MCs) are resident tissue cells that also express CCR3. In the present study, we demonstrate that human (h) MCs in nasal polyps and cultured cord blood-derived...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0155OC
更新日期:2003-04-01 00:00:00
abstract::Recent studies have indicated that, during the development of pulmonary hypertension (PH), there is a switch from oxidative phosphorylation to glycolysis in the pulmonary endothelium. However, the mechanisms underlying this phenomenon have not been elucidated. Endothelin (ET)-1, an endothelial-derived vasoconstrictor ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0187OC
更新日期:2014-06-01 00:00:00
abstract::Epidemiologic studies have linked gestational vitamin D deficiency to respiratory diseases, although mechanisms have not been defined. We hypothesized that antenatal vitamin D deficiency would impair airway development and alveolarization in a mouse model. We studied the effect of antenatal vitamin D deficiency by ind...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2014-0482OC
更新日期:2017-03-01 00:00:00
abstract::In this study we examined the effect of oral antigen (Ag) administration on the development of experimental asthma in different mouse strains. We selected BALB/c, BP2, CBA/Ca interleukin (IL)-5 transgenic, and BALB/c T-cell receptor-delta-deficient mouse strains because they exhibit different aspects of the asthma syn...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.24.5.4320
更新日期:2001-05-01 00:00:00
abstract::Previous observations by our laboratory indicate that the presence of anti-IL-8 autoantibody:IL-8 immune complexes in lung fluids from patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) comprises an important prognostic indicator in the development and ultimate outcome of ALI/ARDS. We also ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0039OC
更新日期:2013-02-01 00:00:00
abstract::Asbestos causes asbestosis and malignancies by mechanisms that are not fully established. Alveolar epithelial cell (AEC) injury and repair are crucial determinants of the fibrogenic potential of noxious agents such as asbestos. We previously showed that mitochondrial reactive oxygen species mediate asbestos-induced AE...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2014-0038OC
更新日期:2015-01-01 00:00:00
abstract::Mechanical ventilation with high tidal volumes has been associated with pulmonary alveolar flooding. Understanding the mechanisms underlying cyclic stretch-induced increases in alveolar epithelial permeability may be important in designing preventive measures for acute lung injury. In this work, we assessed whether cy...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0252OC
更新日期:2013-07-01 00:00:00
abstract::Surfactant protein D (SP-D) is a collagenous, surfactant-associated, carbohydrate-binding protein that is synthesized by pulmonary epithelial cells. In the present studies, we examined the expression of SP-D and SP-D mRNA during late fetal (day 17, 19, 21) and early postnatal (day 5) rat lung development using immunoc...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/5.1.13
更新日期:1991-07-01 00:00:00
abstract::Substantial challenges remain in our understanding of fibrotic lung diseases. Nowhere is this more true than in the elucidation and verification of the pathogenetic basis upon which they develop. Scientific progress, most recently in the field of experimental therapy, has relied closely on interpreting data derived fr...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章,评审
doi:10.1165/rcmb.2005-0062TR
更新日期:2005-07-01 00:00:00
abstract::To identify relationships amongst tracheal and alveolar epithelial cells during lung development, we used conditional systems controlled by the rat CCSP and human SFTPC gene promoters to express Cre-recombinase in the developing mouse lung, thereby permanently labeling cells by expression of alkaline phosphatase or gr...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0180OC
更新日期:2005-11-01 00:00:00
abstract::We investigated the effects of hypoxia (< 2.5% O2) on rat manganese superoxide dismutase (MnSOD) gene promoter-luciferase reporter constructs in transiently transfected lung epithelial cells (A549, L2, and E1A-T2) and fibroblasts (R9Ab). We cloned MnSOD promoter-luciferase reporter constructs (numbers refer to length ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.21.1.3521
更新日期:1999-07-01 00:00:00
abstract::In bronchial asthma, eosinophils found in the airways have an enhanced inflammatory capacity. We hypothesized that, at least in part, changes in functional phenotype are due to the effect of transendothelial migration. To model in vivo eosinophil trafficking to the lung, we cultured human pulmonary microvascular endot...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.3.3707
更新日期:2000-09-01 00:00:00
abstract::The mechanisms used by alveolar type I pneumocytes for maintenance of the lipid homeostasis necessary to sustain these large squamous cells are unknown. The processes may involve the ATP-binding cassette transporter A1 (ABCA1), a transport protein shown to be crucial in apolipoprotein A-I (apoA-I)-mediated mobilizatio...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0020OC
更新日期:2008-03-01 00:00:00
abstract::Neutrophils were found to demonstrate chemotactic responses to pepsinized human placental type IV collagen and its purified aminoterminal 7S domain. The maximal chemotactic responses occur at approximately 400 ng/ml and approximately 30 ng/ml of type IV collagen and 7S collagen, respectively, and are similar in magnit...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/1.6.479
更新日期:1989-12-01 00:00:00
abstract::Although neutrophil migration from the systemic circulation involves the beta2- (or CD18) integrin family, the existence of an alternative, CD18-independent route of neutrophil extravasation to tissues has been demonstrated in animal models. The molecular interactions involved in this alternative migratory route have ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.2.3853
更新日期:2000-08-01 00:00:00
abstract::Transplantation of mesenchymal stem cells (MSCs) holds great promise in the repair of cigarette smoke (CS)-induced lung damage in chronic obstructive pulmonary disease (COPD). Because CS leads to mitochondrial dysfunction, we aimed to investigate the potential benefit of mitochondrial transfer from human-induced pluri...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0529OC
更新日期:2014-09-01 00:00:00
abstract::PS-341 is a highly selective and potent proteasome inhibitor that is cytotoxic to various types of cancer. However, no objective response was seen in a clinical trial with PS-341 as a single agent in non-small cell lung cancer. Its antitumor activity is limited by the simultaneously activated antiapoptosis pathway. Re...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2014-0186OC
更新日期:2015-09-01 00:00:00
abstract::Bronchiolitis obliterans (BO) is an increasingly important lung disease characterized by fibroproliferative airway lesions and decrements in lung function. Occupational exposure to the artificial food flavoring ingredient diacetyl, commonly used to impart a buttery flavor to microwave popcorn, has been associated with...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0372OC
更新日期:2017-06-01 00:00:00
abstract::Cellular senescence has been implicated in diverse pathologies. However, there is conflicting evidence regarding the role of this process in tissue fibrosis. Although dysregulation of microRNAs is a key mechanism in the pathogenesis of lung fibrosis, it is unclear whether microRNAs function by regulating cellular sene...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0163OC
更新日期:2017-02-01 00:00:00
abstract::Endothelin-1 (ET-1) exerts many biological effects in airways, including bronchoconstriction, airway mucus secretion, cell proliferation, and inflammation. We investigated the effect of ET-1 on Na absorption and Cl secretion in human bronchial epithelial cells. Addition of 10(-7) M ET-1 had no effect on the inhibition...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0104OC
更新日期:2003-08-01 00:00:00