Legionella pneumophila induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages.


BACKGROUND:Legionella pneumophila (LPN) can cause a lethal infectious disease with a marked inflammatory response in humans. However, the mechanism of this severe inflammation remains poorly understood. Since necrosis is known to induce inflammation, we investigated whether LPN induces necrosis in macrophages. We also analyzed the involvement of lysosomal cathepsin B in LPN-induced cell death. METHODS:The human monocytic cell line THP-1 was infected with LPN, NUL1 strain. MG132-treated cells were used as apoptotic control cells. After infection, the type of cell death was analyzed by using microscopy, LDH release and flow cytometry. As a proinflammatory mediator, high-mobility group box 1 (HMGB-1), was measured. Cathepsin B activity was also measured and the inhibitory effects of cathepsin B on LPN-induced cell death were analyzed. RESULTS:THP-1 cells after treatment with high dose of LPN showed necrotic features with releasing HMGB-1. This necrosis and the HMGB-1 release were inhibited by a specific lysosomal cathepsin B inhibitor and were characterized by a rapid and high activation of cathepsin B that was not observed in apoptotic control cells. The necrosis was also accompanied by cathepsin B-dependent poly(ADP-ribose) polymerase (PARP) cleavage. CONCLUSIONS:We demonstrate here that L. pneumophila rapidly induces cathepsin B-dependent necrosis in a dose-dependent manner and releases a proinflammatory mediator, HMGB-1, from macrophages. This report describes a novel aspect of the pathogenesis of Legionnaires' disease and provides a possible therapeutic target for the regulation of inflammation.


Respir Res


Respiratory research


Morinaga Y,Yanagihara K,Nakamura S,Hasegawa H,Seki M,Izumikawa K,Kakeya H,Yamamoto Y,Yamada Y,Kohno S,Kamihira S




Has Abstract


2010-11-22 00:00:00












  • Examining the role of ABC lipid transporters in pulmonary lipid homeostasis and inflammation.

    abstract::Respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD) are characterised by excessive and persistent inflammation. Current treatments are often inadequate for symptom and disease control, and hence new therapies are warranted. Recent emerging research has implicated dyslipidaemia in pul...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Chai AB,Ammit AJ,Gelissen IC

    更新日期:2017-02-28 00:00:00

  • Incidence of asthma and mortality in a cohort of young adults: a 7-year prospective study.

    abstract:BACKGROUND:Few longitudinal data exist on the incidence of asthma in young adults and on the overall mortality risk due to asthma. A 7-year follow-up prospective study was performed to assess the incidence of asthma and mortality from all causes in a cohort of young adults. METHODS:The life status of a cohort of 6031 ...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章


    authors: de Marco R,Locatelli F,Cazzoletti L,Bugianio M,Carosso A,Marinoni A

    更新日期:2005-08-16 00:00:00

  • A retinoid X receptor partial agonist attenuates pulmonary emphysema and airway inflammation.

    abstract:BACKGROUND:Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signalling by 9-cis retinoic acid, a vitamin A derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners, e.g., for retinoic acid receptors, vitamin D receptors, and peroxisome prolif...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Morichika D,Miyahara N,Fujii U,Taniguchi A,Oda N,Senoo S,Kataoka M,Tanimoto M,Kakuta H,Kiura K,Maeda Y,Kanehiro A

    更新日期:2019-01-03 00:00:00

  • Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model.

    abstract:BACKGROUND:Emphysema is a crucial pathological characteristic of chronic obstructive pulmonary disease (COPD). Oxidative stress, apoptosis and epigenetic mechanisms contribute to the pathogenesis of emphysema. However, an attempt to accurately identify whether these mechanisms interact with each other and how they are ...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Zeng H,Li T,He X,Cai S,Luo H,Chen P,Chen Y

    更新日期:2020-09-03 00:00:00

  • Cell-specific expression of lung disease risk-related genes in the human small airway epithelium.

    abstract:BACKGROUND:The human small airway epithelium (SAE) plays a central role in the early events in the pathogenesis of most inherited and acquired lung disorders. Little is known about the molecular phenotypes of the specific cell populations comprising the SAE in humans, and the contribution of SAE specific cell populatio...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Zuo WL,Rostami MR,Shenoy SA,LeBlanc MG,Salit J,Strulovici-Barel Y,O'Beirne SL,Kaner RJ,Leopold PL,Mezey JG,Schymeinsky J,Quast K,Visvanathan S,Fine JS,Thomas MJ,Crystal RG

    更新日期:2020-07-29 00:00:00

  • Neurotrophins and neurotrophin receptors in pulmonary sarcoidosis - granulomas as a source of expression.

    abstract:BACKGROUND:Pulmonary sarcoidosis is an inflammatory disease, characterized by an accumulation of CD4+ lymphocytes and the formation of non-caseating epithelioid cell granulomas in the lungs. The disease either resolves spontaneously or develops into a chronic disease with fibrosis. The neurotrophins nerve growth factor...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Dagnell C,Grunewald J,Kramar M,Haugom-Olsen H,Elmberger GP,Eklund A,Olgart Höglund C

    更新日期:2010-11-08 00:00:00

  • Gender and respiratory factors associated with dyspnea in chronic obstructive pulmonary disease.

    abstract:RATIONALE:We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction. OBJECTIVES:Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients. METHODS:In a FEV1 % matched population of 100 men and women with COPD we measured: age, MMRC, FEV1, ...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: de Torres JP,Casanova C,Montejo de Garcini A,Aguirre-Jaime A,Celli BR

    更新日期:2007-03-06 00:00:00

  • The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide.

    abstract:BACKBROUND:COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfi...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Perry MM,Tildy B,Papi A,Casolari P,Caramori G,Rempel KL,Halayko AJ,Adcock I,Chung KF

    更新日期:2018-05-09 00:00:00

  • Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study.

    abstract:BACKGROUND:Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile ...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验


    authors: Lamarche D,Johnstone J,Zytaruk N,Clarke F,Hand L,Loukov D,Szamosi JC,Rossi L,Schenck LP,Verschoor CP,McDonald E,Meade MO,Marshall JC,Bowdish DME,Karachi T,Heels-Ansdell D,Cook DJ,Surette MG,PROSPECT Investigators.,C

    更新日期:2018-12-07 00:00:00

  • Real world evaluation of a novel lateral flow assay (AlphaKit® QuickScreen) for the detection of alpha-1-antitrypsin deficiency.

    abstract:BACKGROUND:Alpha-1-Antitrypsin (AAT) deficiency (AATD) is a hereditary disorder that manifests primarily as pulmonary emphysema and liver cirrhosis. The clinically most relevant mutation causing AATD is a single nucleotide polymorphism Glu342Lys (Z-mutation). Despite the recommendation to test every COPD patient, the c...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究


    authors: Greulich T,Rodríguez-Frias F,Belmonte I,Klemmer A,Vogelmeier CF,Miravitlles M

    更新日期:2018-08-13 00:00:00

  • Weighted Epworth sleepiness scale predicted the apnea-hypopnea index better.

    abstract:BACKGROUND:The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS it...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Guo Q,Song WD,Li W,Zeng C,Li YH,Mo JM,Lü ZD,Jiang M

    更新日期:2020-06-12 00:00:00

  • Sex-specific lung functional changes in adult mice exposed only to second-hand smoke in utero.

    abstract:BACKGROUND:An increasing number of epidemiological and experimental studies have associated exposure to second-hand smoke (SHS) during pregnancy with adverse outcomes in newborns. As we have previously shown in mice, in utero exposure to SHS at critical stages of fetal development, results in altered lung responses and...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Noël A,Xiao R,Perveen Z,Zaman H,Le Donne V,Penn A

    更新日期:2017-06-27 00:00:00

  • Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension.

    abstract:BACKGROUND:The development of bronchial hyperreactivity (BHR) subsequent to precapillary pulmonary hypertension (PHT) was prevented by acting on the major signalling pathways (endothelin, nitric oxide, vasoactive intestine peptide (VIP) and prostacyclin) involved in the control of the pulmonary vascular and bronchial t...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Habre W,Albu G,Janosi TZ,Fontao F,von Ungern-Sternberg BS,Beghetti M,Petak F

    更新日期:2011-04-27 00:00:00

  • Perip7lakin is a target for autoimmunity in asthma.

    abstract::The role of autoimmunity targeting epithelial antigens in asthma has been suggested, in particular in non-atopic and severe asthma. Periplakin, a desmosomal component, is involved in epithelial cohesion and intracellular signaling. We detected anti-periplakin IgG antibodies in 47/260 (18 %) patients with asthma, with ...

    journal_title:Respiratory research

    pub_type: 信件


    authors: Taillé C,Grootenboer-Mignot S,Estellat C,Roy C,Ly Ka So S,Pretolani M,Aubier M,Crestani B,Chollet-Martin S

    更新日期:2016-10-07 00:00:00

  • Artificial intelligence accuracy in detecting pathological breath sounds in children using digital stethoscopes.

    abstract:BACKGROUND:Manual auscultation to detect abnormal breath sounds has poor inter-observer reliability. Digital stethoscopes with artificial intelligence (AI) could improve reliable detection of these sounds. We aimed to independently test the abilities of AI developed for this purpose. METHODS:One hundred and ninety two...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Kevat A,Kalirajah A,Roseby R

    更新日期:2020-09-29 00:00:00

  • Rate of progression of CT-quantified emphysema in male current and ex-smokers: a follow-up study.

    abstract:BACKGROUND:Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers. M...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验


    authors: Mohamed Hoesein FA,Zanen P,de Jong PA,van Ginneken B,Boezen HM,Groen HJ,Oudkerk M,de Koning HJ,Postma DS,Lammers JW

    更新日期:2013-05-20 00:00:00

  • DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease.

    abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in ...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Lee JH,McDonald ML,Cho MH,Wan ES,Castaldi PJ,Hunninghake GM,Marchetti N,Lynch DA,Crapo JD,Lomas DA,Coxson HO,Bakke PS,Silverman EK,Hersh CP,COPDGene and ECLIPSE Investigators.

    更新日期:2014-08-20 00:00:00

  • Signaling and regulation of G protein-coupled receptors in airway smooth muscle.

    abstract::Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that ...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Billington CK,Penn RB

    更新日期:2003-01-01 00:00:00

  • Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8(+) T cells in chronic obstructive pulmonary disease.

    abstract:BACKGROUND:Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder. COPD is characterized by an increase in CD8(+) T cells within the central and peripheral airways. We hypothesized that the CD8(+) T cells in COPD patients have increased Toll-like receptor ...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Nadigel J,Préfontaine D,Baglole CJ,Maltais F,Bourbeau J,Eidelman DH,Hamid Q

    更新日期:2011-11-09 00:00:00

  • Add-on therapy options in asthma not adequately controlled by inhaled corticosteroids: a comprehensive review.

    abstract::Many patients with persistent asthma can be controlled with inhaled corticosteroids (ICS). However, a considerable proportion of patients remain symptomatic, despite the use of ICS. We present systematically evidence that supports the different treatment options. A literature search was made of Medline/PubMed to ident...

    journal_title:Respiratory research

    pub_type: 杂志文章,meta分析,评审


    authors: Kankaanranta H,Lahdensuo A,Moilanen E,Barnes PJ

    更新日期:2004-10-27 00:00:00

  • Role and regulation of Abelson tyrosine kinase in Crk-associated substrate/profilin-1 interaction and airway smooth muscle contraction.

    abstract:BACKGROUND:Airway smooth muscle contraction is critical for maintenance of appropriate airway tone, and has been implicated in asthma pathogenesis. Smooth muscle contraction requires an "engine" (myosin activation) and a "transmission system" (actin cytoskeletal remodeling). However, the mechanisms that control actin r...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Wang Y,Rezey AC,Wang R,Tang DD

    更新日期:2018-01-05 00:00:00

  • Glucocorticoid receptor gene polymorphisms associated with progression of lung disease in young patients with cystic fibrosis.

    abstract:BACKGROUND:The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to var...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究


    authors: Corvol H,Nathan N,Charlier C,Chadelat K,Le Rouzic P,Tabary O,Fauroux B,Henrion-Caude A,Feingold J,Boelle PY,Clement A

    更新日期:2007-11-29 00:00:00

  • Serum biomarkers in interstitial lung diseases.

    abstract::The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The pas...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Tzouvelekis A,Kouliatsis G,Anevlavis S,Bouros D

    更新日期:2005-07-21 00:00:00

  • Factors associated with change in exacerbation frequency in COPD.

    abstract:BACKGROUND:Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to year, some wi...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章


    authors: Donaldson GC,Müllerova H,Locantore N,Hurst JR,Calverley PM,Vestbo J,Anzueto A,Wedzicha JA

    更新日期:2013-07-30 00:00:00

  • CD8 positive T cells express IL-17 in patients with chronic obstructive pulmonary disease.

    abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease of the lung. The nature of the immune reaction in COPD raises the possibility that IL-17 and related cytokines may contribute to this disorder. This study analyzed the expression of IL-17A and IL-17F a...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Chang Y,Nadigel J,Boulais N,Bourbeau J,Maltais F,Eidelman DH,Hamid Q

    更新日期:2011-04-10 00:00:00

  • LPS induces IL-10 production by human alveolar macrophages via MAPKinases- and Sp1-dependent mechanisms.

    abstract:BACKGROUND:IL-10 is a cytokine mainly produced by macrophages that plays key roles in tolerance to inhaled antigens and in lung homeostasis. Its regulation in alveolar macrophages (HAM), the resident lung phagocytes, remains however unknown. METHODS:The present study investigated the role of intracellular signalling a...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Chanteux H,Guisset AC,Pilette C,Sibille Y

    更新日期:2007-10-04 00:00:00

  • The unsynchronized changes of CT image and nucleic acid detection in COVID-19: reports the two cases from Gansu, China.

    abstract::The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been co...

    journal_title:Respiratory research

    pub_type: 信件


    authors: Gao J,Liu JQ,Wen HJ,Liu H,Hu WD,Han X,Li CX,Wang XJ

    更新日期:2020-04-22 00:00:00

  • Impact of Mycobacterium tuberculosis complex lineages as a determinant of disease phenotypes from an immigrant rich moderate tuberculosis burden country.

    abstract:BACKGROUND:Growing evidences suggested that the Mycobacterium tuberculosis complex (MTBC) lineages can determine the clinical outcome of pulmonary and extra-pulmonary tuberculosis. However, limited data only available revealing such association of bacterial genotypes and clinical phenotypes from immigrant rich countrie...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究


    authors: Varghese B,Enani M,Alrajhi A,Al Johani S,Albarak A,Althawadi S,Elkhizzi N,AlGhafli H,Shoukri M,Al-Hajoj S

    更新日期:2018-12-27 00:00:00

  • Oxygen-regulated transcription factors and their role in pulmonary disease.

    abstract::The transcription factors nuclear factor interleukin-6 (NF-IL6), early growth response-1 (EGR-1) and hypoxia-inducible factor-1 (HIF-1) have important roles in the molecular pathophysiology of hypoxia-associated pulmonary disease. NF-IL6 controls the production of interleukin (IL)-6 in vascular endothelial cells, whic...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Semenza GL

    更新日期:2000-01-01 00:00:00

  • Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella pneumoniae in mice.

    abstract:BACKGROUND:Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia. METHODS:C57BL/6 mice received daily, nose-...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Patterson CM,Morrison RL,D'Souza A,Teng XS,Happel KI

    更新日期:2012-05-31 00:00:00