Lymphocyte senescence in COPD is associated with loss of glucocorticoid receptor expression by pro-inflammatory/cytotoxic lymphocytes.

Abstract:

BACKGROUND:Glucocorticoid (GC) resistance is a major barrier in COPD treatment. We have shown increased expression of the drug efflux pump, Pgp1 in cytotoxic/pro-inflammatory lymphocytes in COPD. Loss of lymphocyte co-stimulatory molecule CD28 (lymphocyte senescence) was associated with a further increase in their pro-inflammatory/cytotoxic potential and resistance to GC. We hypothesized that lymphocyte senescence and increased Pgp1 are also associated with down-regulation of the GC receptor (GCR). METHODS:Blood was collected from 10 COPD and 10 healthy aged-matched controls. Flow cytometry was applied to assess intracellular pro-inflammatory cytokines, CD28, Pgp1, GCR, steroid binding and relative cytoplasm/nuclear GCR by CD28+ and CD28null T, NKT-like cells. GCR localization was confirmed by fluorescent microscopy. RESULTS:COPD was associated with increased numbers of CD28nullCD8+ T and NKT-like cells. Loss of CD28 was associated with an increased percentage of T and NKT-like cells producing IFNγ or TNFα and associated with a loss of GCR and Dex-Fluor staining but unchanged Pgp1. There was a significant loss of GCR in CD8 + CD28null compared with CD8 + CD28+ T and NKT-like cells from both COPD and controls (eg, mean ± SEM 8 ± 3% GCR + CD8 + CD28null T-cells vs 49 ± 5% GCR + CD8 + CD28+ T-cells in COPD). There was a significant negative correlation between GCR expression and IFNγ and TNFα production by T and NKT-like cells(eg, COPD: T-cell IFNγ R = -.615; ) and with FEV1 in COPD (R = -.777). CONCLUSIONS:COPD is associated with loss of GCR in senescent CD28null and NKT-like cells suggesting alternative treatment options to GC are required to inhibit these pro-inflammatory/cytotoxic cells.

journal_name

Respir Res

journal_title

Respiratory research

authors

Hodge G,Jersmann H,Tran HB,Holmes M,Reynolds PN,Hodge S

doi

10.1186/s12931-014-0161-7

subject

Has Abstract

pub_date

2015-01-09 00:00:00

pages

2

eissn

1465-9921

issn

1465-993X

pii

s12931-014-0161-7

journal_volume

16

pub_type

杂志文章
  • Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis.

    abstract:BACKGROUND:Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and ...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究

    doi:10.1186/1465-9921-15-27

    authors: Aliberti S,Brambilla AM,Chalmers JD,Cilloniz C,Ramirez J,Bignamini A,Prina E,Polverino E,Tarsia P,Pesci A,Torres A,Blasi F,Cosentini R

    更新日期:2014-03-04 00:00:00

  • Heterogeneous burden of lung disease in smokers with borderline airflow obstruction.

    abstract:BACKGROUND:The identification of smoking-related lung disease in current and former smokers with normal FEV1 is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of ai...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究

    doi:10.1186/s12931-018-0911-z

    authors: Pirozzi CS,Gu T,Quibrera PM,Carretta EE,Han MK,Murray S,Cooper CB,Tashkin DP,Kleerup EC,Barjaktarevic I,Hoffman EA,Martinez CH,Christenson SA,Hansel NN,Graham Barr R,Bleecker ER,Ortega VE,Martinez FJ,Kanner RE,Paine

    更新日期:2018-11-20 00:00:00

  • Allergen particle binding by human primary bronchial epithelial cells is modulated by surfactant protein D.

    abstract:BACKGROUND:Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. Our previous work demonstrated that SP-D increase...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-11-83

    authors: Schleh C,Erpenbeck VJ,Winkler C,Lauenstein HD,Nassimi M,Braun A,Krug N,Hohlfeld JM

    更新日期:2010-06-22 00:00:00

  • The unique alterations of hippocampus and cognitive impairment in chronic obstructive pulmonary disease.

    abstract:BACKGROUND:Cognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients. However, the structural alteration of the brain and underlying mechanisms are poorly understood. METHODS:Thirty-seven mild-to-moderate COPD patients, forty-eight severe COPD patients, and thirty-one control subject...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-14-140

    authors: Li J,Fei GH

    更新日期:2013-12-21 00:00:00

  • Therapeutic effect of budesonide/formoterol, montelukast and N-acetylcysteine for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation.

    abstract:BACKGROUND:Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which a...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-016-0380-1

    authors: Kim SW,Rhee CK,Kim YJ,Lee S,Kim HJ,Lee JW

    更新日期:2016-05-26 00:00:00

  • Hospitalisation and mortality in patients with comorbid COPD and heart failure: a systematic review and meta-analysis.

    abstract:BACKGROUND:Discrepancy exists amongst studies investigating the effect of comorbid heart failure (HF) on the morbidity and mortality of chronic obstructive pulmonary disease (COPD) patients. METHODS:MEDLINE and Embase were searched using a pre-specified search strategy for studies comparing hospitalisation, rehospital...

    journal_title:Respiratory research

    pub_type: 杂志文章,meta分析

    doi:10.1186/s12931-020-1312-7

    authors: Axson EL,Ragutheeswaran K,Sundaram V,Bloom CI,Bottle A,Cowie MR,Quint JK

    更新日期:2020-02-14 00:00:00

  • Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations.

    abstract:BACKGROUND:Asthma is a heterogeneous chronic airway disease, which may be classified into different phenotypes. YKL-40 is a chitin-binding glycoprotein with unclear functions, but its expression is associated with inflammation and tissue remodeling. However, few studies have explored whether YKL-40 is associated with i...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-019-1051-9

    authors: Liu L,Zhang X,Liu Y,Zhang L,Zheng J,Wang J,Hansbro PM,Wang L,Wang G,Hsu AC

    更新日期:2019-05-22 00:00:00

  • Bidirectional role of IL-6 signal in pathogenesis of lung fibrosis.

    abstract:BACKGROUND:Various signals are known to participate in the pathogenesis of lung fibrosis. Our aim was to determine which signal is predominantly mobilized in the early inflammatory phase and thereafter modulates the development of lung fibrosis. METHODS:Mice received a single dose of 3 mg/kg body weight of bleomycin (...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-015-0261-z

    authors: Kobayashi T,Tanaka K,Fujita T,Umezawa H,Amano H,Yoshioka K,Naito Y,Hatano M,Kimura S,Tatsumi K,Kasuya Y

    更新日期:2015-08-20 00:00:00

  • The importance of balanced pro-inflammatory and anti-inflammatory mechanisms in diffuse lung disease.

    abstract::The lung responds to a variety of insults in a remarkably consistent fashion but with inconsistent outcomes that vary from complete resolution and return to normal to the destruction of normal architecture and progressive fibrosis. Increasing evidence indicates that diffuse lung disease results from an imbalance betwe...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审

    doi:10.1186/rr177

    authors: Keane MP,Strieter RM

    更新日期:2002-01-01 00:00:00

  • Determination of rheology and surface tension of airway surface liquid: a review of clinical relevance and measurement techniques.

    abstract::By airway surface liquid, we mean a thin fluid continuum consisting of the airway lining layer and the alveolar lining layer, which not only serves as a protective barrier against foreign particles but also contributes to maintaining normal respiratory mechanics. In recent years, measurements of the rheological proper...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审

    doi:10.1186/s12931-019-1229-1

    authors: Chen Z,Zhong M,Luo Y,Deng L,Hu Z,Song Y

    更新日期:2019-12-04 00:00:00

  • Responses of FEV6, FVC, and FET to inhaled bronchodilator in the adult general population.

    abstract:BACKGROUND:The assessment of bronchodilator-induced change in forced vital capacity (FVC) is dependent on forced expiratory time (FET) in subjects with airflow limitation. Limited information is available on the concurrent responses of FVC, forced expiratory volume in six seconds (FEV6), and FET in the bronchodilation ...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-10-71

    authors: Kainu A,Lindqvist A,Sarna S,Lundbäck B,Sovijärvi A

    更新日期:2009-07-28 00:00:00

  • Approach to diagnosis and pathological examination in bronchial Dieulafoy disease: a case series.

    abstract:BACKGROUND:There are limited series concerning Dieulafoy disease of the bronchus. We describe the clinical presentation of a series of 7 patients diagnosed with Dieulafoy disease of the bronchus and provide information about the pathological diagnosis approach. PATIENTS AND METHODS:A retrospective review of patients w...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-9-58

    authors: Parrot A,Antoine M,Khalil A,Théodore J,Mangiapan G,Bazelly B,Fartoukh M

    更新日期:2008-08-05 00:00:00

  • Successful establishment of primary small airway cell cultures in human lung transplantation.

    abstract:BACKGROUND:The study of small airway diseases such as post-transplant bronchiolitis obliterans syndrome (BOS) is hampered by the difficulty in assessing peripheral airway function either physiologically or directly. Our aims were to develop robust methods for sampling small airway epithelial cells (SAEC) and to establi...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-10-99

    authors: Banerjee B,Kicic A,Musk M,Sutanto EN,Stick SM,Chambers DC

    更新日期:2009-10-26 00:00:00

  • Sputum and blood transcriptomics characterisation of the inhaled PDE4 inhibitor CHF6001 on top of triple therapy in patients with chronic bronchitis.

    abstract:BACKGROUND:Although phosphodiesterase-4 (PDE4) inhibitors have been shown to reduce COPD exacerbation rate, their biological mechanism of action is not completely elucidated at the molecular level. We aimed to characterise the whole genome gene expression profile of the inhaled PDE4-inhibitor CHF6001 on top of triple t...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1186/s12931-020-1329-y

    authors: Govoni M,Bassi M,Vezzoli S,Lucci G,Emirova A,Nandeuil MA,Petruzzelli S,Jellema GL,Afolabi EK,Colgan B,Leaker B,Kornmann O,Beeh KM,Watz H,Singh D

    更新日期:2020-03-20 00:00:00

  • Prenatal fine particulate exposure associated with reduced childhood lung function and nasal epithelia GSTP1 hypermethylation: Sex-specific effects.

    abstract:BACKGROUND:In utero exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) has been linked to child lung function. Overlapping evidence suggests that child sex and exposure timing may modify effects and associations may be mediated through glutathione S-transferase P1 (GSTP1) methylatio...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-018-0774-3

    authors: Lee AG,Le Grand B,Hsu HL,Chiu YM,Brennan KJ,Bose S,Rosa MJ,Brunst KJ,Kloog I,Wilson A,Schwartz J,Morgan W,Coull BA,Wright RO,Baccarelli AA,Wright RJ

    更新日期:2018-04-27 00:00:00

  • Lung function reductions associated with motor vehicle density in chronic obstructive pulmonary disease: a cross-sectional study.

    abstract:BACKGROUND:Motor vehicle-related air pollution can potentially impair lung function. The effect of pollution in people with compromised pulmonary function such as in COPD has not been previously investigated. To examine the association of lung function with motor vehicle density in people with spirometrically determine...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-016-0451-3

    authors: Nitschke M,Appleton SL,Li Q,Tucker GR,Shah P,Bi P,Pisaniello DL,Adams RJ

    更新日期:2016-10-24 00:00:00

  • Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension.

    abstract:BACKGROUND:Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants....

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/s12931-019-1180-1

    authors: White RJ,Vonk-Noordegraaf A,Rosenkranz S,Oudiz RJ,McLaughlin VV,Hoeper MM,Grünig E,Ghofrani HA,Chakinala MM,Barberà JA,Blair C,Langley J,Frost AE

    更新日期:2019-09-12 00:00:00

  • Regulation of ATP binding cassette transporter A1 (ABCA1) expression: cholesterol-dependent and - independent signaling pathways with relevance to inflammatory lung disease.

    abstract::The role of the ATP binding cassette transporter A1 (ABCA1) in maintaining cellular lipid homeostasis in cardiovascular disease is well established. More recently, the important beneficial role played by ABCA1 in modulating pathogenic disease mechanisms, such as inflammation, in a broad range of chronic conditions has...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审

    doi:10.1186/s12931-020-01515-9

    authors: He P,Gelissen IC,Ammit AJ

    更新日期:2020-09-25 00:00:00

  • Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs.

    abstract:BACKGROUND:Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investig...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-13-103

    authors: Shimodaira K,Okubo Y,Ochiai E,Nakayama H,Katano H,Wakayama M,Shinozaki M,Ishiwatari T,Sasai D,Tochigi N,Nemoto T,Saji T,Kamei K,Shibuya K

    更新日期:2012-11-17 00:00:00

  • Macrorheology of cystic fibrosis, chronic obstructive pulmonary disease & normal sputum.

    abstract:BACKGROUND:Prior microrheologic assessments of selected, microlitre plugs of cystic fibrosis (CF) sputum suggest no intrinsic rheologic abnormality. However, such analyses may not be representative of CF sputum as a whole. We therefore reassessed this question using whole sputum macrorheology. Additionally, we wished t...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-10-63

    authors: Serisier DJ,Carroll MP,Shute JK,Young SA

    更新日期:2009-07-06 00:00:00

  • Surfactant protein D attenuates sub-epithelial fibrosis in allergic airways disease through TGF-β.

    abstract:BACKGROUND:Surfactant protein D (SP-D) can regulate both innate and adaptive immunity. Recently, SP-D has been shown to contribute to the pathogenesis of airway allergic inflammation and bleomycin-induced pulmonary fibrosis. However, in allergic airways disease, the role of SP-D in airway remodeling remains unknown. Th...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-014-0143-9

    authors: Ogawa H,Ledford JG,Mukherjee S,Aono Y,Nishioka Y,Lee JJ,Izumi K,Hollingsworth JW

    更新日期:2014-11-29 00:00:00

  • Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment.

    abstract:BACKGROUND:Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantita...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/1465-9921-12-124

    authors: O'Neil SE,Sitkauskiene B,Babusyte A,Krisiukeniene A,Stravinskaite-Bieksiene K,Sakalauskas R,Sihlbom C,Ekerljung L,Carlsohn E,Lötvall J

    更新日期:2011-09-22 00:00:00

  • Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses.

    abstract:BACKGROUND:Influenza virus binds to cell receptors via sialic acid (SA) linked glycoproteins. They recognize SA on host cells through their haemagglutinins (H). The distribution of SA on cell surfaces is one determinant of host tropism and understanding its expression on human cells and tissues is important for underst...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-8-73

    authors: Nicholls JM,Bourne AJ,Chen H,Guan Y,Peiris JS

    更新日期:2007-10-25 00:00:00

  • Pathophysiological classification of chronic rhinosinusitis.

    abstract:BACKGROUND:Recent consensus statements demonstrate the breadth of the chronic rhinosinusitis (CRS) differential diagnosis. However, the classification and mechanisms of different CRS phenotypes remains problematic. METHOD:Statistical patterns of subjective and objective findings were assessed by retrospective chart re...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-6-149

    authors: Baraniuk JN,Maibach H

    更新日期:2005-12-19 00:00:00

  • Decreased expression of the NF-κB family member RelB in lung fibroblasts from Smokers with and without COPD potentiates cigarette smoke-induced COX-2 expression.

    abstract:BACKGROUND:Heightened inflammation, including expression of COX-2, is associated with COPD pathogenesis. RelB is an NF-κB family member that attenuates COX-2 in response to cigarette smoke by a mechanism that may involve the miRNA miR-146a. There is no information on the expression of RelB in COPD or if RelB prevents C...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-015-0214-6

    authors: Sheridan JA,Zago M,Nair P,Li PZ,Bourbeau J,Tan WC,Hamid Q,Eidelman DH,Benedetti AL,Baglole CJ

    更新日期:2015-05-06 00:00:00

  • Differences in the risk of mood disorders in patients with asthma-COPD overlap and in patients with COPD alone: a nationwide population-based retrospective cohort study in Korea.

    abstract:BACKGROUND:Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), little is known about the estimates of their incidence in patients with asthma-COPD overlap (ACO), which has been described and acknowledged as a distinct clinical entity. We aimed to estimat...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-019-1039-5

    authors: Kang HR,Hong SH,Ha SY,Kim TB,Lee EK

    更新日期:2019-04-30 00:00:00

  • Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.

    abstract:BACKGROUND:CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known. ...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-6-25

    authors: Matheu V,Treschow A,Teige I,Navikas V,Issazadeh-Navikas S

    更新日期:2005-03-05 00:00:00

  • Snoring in primary school children and domestic environment: a Perth school based study.

    abstract:BACKGROUND:The home is the predominant environment for exposure to many environmental irritants such as air pollutants and allergens. Exposure to common indoor irritants including volatile organic compounds, formaldehyde and nitrogen dioxide, may increase the risk of snoring for children. The aim of this study was to i...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/1465-9921-5-19

    authors: Zhang G,Spickett J,Rumchev K,Lee AH,Stick S

    更新日期:2004-11-04 00:00:00

  • Pharmacological inhibition of GSK-3 in a guinea pig model of LPS-induced pulmonary inflammation: II. Effects on skeletal muscle atrophy.

    abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is accompanied by pulmonary inflammation and associated with extra-pulmonary manifestations, including skeletal muscle atrophy. Glycogen synthase kinase-3 (GSK-3) has been implicated in the regulation of muscle protein- and myonuclear turnover; two crucial process...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-14-117

    authors: Verhees KJ,Pansters NA,Baarsma HA,Remels AH,Haegens A,de Theije CC,Schols AM,Gosens R,Langen RC

    更新日期:2013-11-01 00:00:00

  • Acquired defects in CFTR-dependent β-adrenergic sweat secretion in chronic obstructive pulmonary disease.

    abstract:RATIONALE:Smoking-induced chronic obstructive pulmonary disease (COPD) is associated with acquired systemic cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Recently, sweat evaporimetry has been shown to efficiently measure β-adrenergic sweat rate and specifically quantify CFTR function in the se...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-15-25

    authors: Courville CA,Tidwell S,Liu B,Accurso FJ,Dransfield MT,Rowe SM

    更新日期:2014-02-25 00:00:00