The specific chymase inhibitor TY-51469 suppresses the accumulation of neutrophils in the lung and reduces silica-induced pulmonary fibrosis in mice.

Abstract:

:Chymase is a chymotrypsin-like serine protease that is present in mast cells. Its activities include various effects associated with inflammatory responses. But little is known about the effects of chymase in pulmonary fibrosis. The mouse silicosis model was induced by intratracheal injection of 10 mg silica. The Ashcroft pathological score and the hydroxyproline content of lungs were measured to evaluate the effect of a chymase inhibitor, 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl] thiazole-4-carboxylic acid (TY-51469). The cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF) were also examined. Following TY-51469 treatment, the lung fibrosis score and hydroxyproline level were significantly reduced, and the number of neutrophils and the levels of macrophage inflammatory protein-2, monocyte chemoattractant protein-1, and transforming growth factor-β₁ in BALF were reduced on day 21. The administration of TY-51469 at an early stage showed a greater reduction of fibrosis compared to administration at a later stage. The neutrophil number in BALF in mice treated with TY-51469 both at an early stage and late stage was significantly reduced. The level of mouse mast cell proteinase-4 mRNA increased with time in silica-induced fibrosing lung tissue. These results show that the chymase inhibitor TY51469 suppresses the migration of neutrophils, which results in the suppression of lung fibrosis.

journal_name

Exp Lung Res

authors

Takato H,Yasui M,Ichikawa Y,Waseda Y,Inuzuka K,Nishizawa Y,Tagami A,Fujimura M,Nakao S

doi

10.3109/01902148.2010.520815

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

101-8

issue

2

eissn

0190-2148

issn

1521-0499

journal_volume

37

pub_type

杂志文章
  • Pulmonary expression of nitric oxide synthase isoforms in sheep with smoke inhalation and burn injury.

    abstract::Previous studies have indicated increased plasma levels of inducible nitric oxide synthase in lung. This study further examines the pulmonary expression of nitric oxide synthase (NOS) isoforms in an ovine model of acute lung injury induced by smoke inhalation and burn injury (S+B injury). Female range bred sheep (4 pe...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/01902140802446832

    authors: Cox RA,Jacob S,Oliveras G,Murakami K,Enkhbaatar P,Traber L,Schmalstieg FC,Herndon DN,Traber DL,Hawkins HK

    更新日期:2009-03-01 00:00:00

  • Indomethacin and flurbiprofen speed recovery of rat bronchial epithelium after exposure to cigarette smoke.

    abstract::The cigarette smoke-induced rat model of chronic bronchitis was used to study the time course of the return of cigarette smoke-induced secretory cell hyperplasia to the normal and the capacity of two non-steroidal anti-inflammatory drugs to speed this recovery. Cigarette smoke alone significantly increased (P less tha...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148609061499

    authors: Rogers DF,Jeffery PK

    更新日期:1986-01-01 00:00:00

  • Factors which affect superoxide anion release from rat alveolar macrophages.

    abstract::In order to investigate some of the characteristics of superoxide anion release from alveolar macrophages, the effects of substances known to influence superoxide release from polymorphonuclear leukocytes (PMN) were studied in rat alveolar macrophages. There is a relatively small, but constant, amount of superoxide re...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148109052305

    authors: Sweeney TD,Castranova V,Bowman L,Miles PR

    更新日期:1981-05-01 00:00:00

  • Platelet-derived growth factor, transforming growth factor-beta, and connective tissue growth factor in a porcine bronchial model of obliterative bronchiolitis.

    abstract::The expression of platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, and connective tissue growth factor (CTGF) and the effect of imatinib, an agent inhibiting PDGF receptors, were assessed in a porcine bronchial transplantation model of obliterative bronchiolitis (OB). Up-regulation of PDGF...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/01902140701539745

    authors: Alho HS,Maasilta PK,Vainikka T,Salminen US

    更新日期:2007-08-01 00:00:00

  • Chronic zinc deficiency induces an antioxidant adaptive response in rat lung.

    abstract::Few studies are available about the role of dietary zinc (Zn) in respiratory diseases. Adult male rats were divided into 2 groups and fed respectively a moderate Zn-deficient diet and a Zn-adequate control diet. In lung tissue at 2 months, thiobarbituric acid-reactive species (TBARS), total glutathione, glutathione di...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/01902140303776

    authors: Gomez NN,Fernandez MR,Zirulnik F,Gil E,Scardapane L,Ojeda MS,Gimenez MS

    更新日期:2003-10-01 00:00:00

  • Leptin up-regulates MUC5B expression in human airway epithelial cells via mitogen-activated protein kinase pathway.

    abstract::Leptin, an adipocyte-secreted hormone that regulates food intake and metabolic response, has been recently reported to increase in the serum during inflammatory airway disease associated with mucus-hypersecretion. We investigated the effects of leptin on mucin expression in human airway epithelial cells and the signal...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902140903427033

    authors: Woo HJ,Yoo WJ,Bae CH,Song SY,Kim YW,Park SY,Kim YD

    更新日期:2010-06-01 00:00:00

  • Characterization of proteoglycans synthesized by fetal rat lung type II pneumonocytes in vitro and the effects of cortisol.

    abstract::The synthesis of proteoglycans by primary cultures of 19-day gestation fetal rat lung Type II pneumonocytes was studied. The cells were grown in the presence of [3H]-glucosamine and/or [35S]-Na2SO4 and the radioactive label incorporated into proteoglycans was analyzed. Proteoglycans of high molecular weight (approxima...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148709064304

    authors: Skinner SJ,Post M,Torday JS,Stiles AD,Smith BT

    更新日期:1987-01-01 00:00:00

  • Eprazinone alters lung lavage lipid levels and transtracheal ion transport.

    abstract::Eprazinone therapy improves pulmonary function and arterial pO2 in patients with chronic bronchitis; however, the mechanism of action is unknown. The purpose of this study was to determine if eprazinone alters either lung surfactant levels in bronchoalveolar lavage fluid (BAL) of normal rats, or ion transport across c...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902149209031693

    authors: Thrall RS,Cloutier MM,Guernsey L,Swayne E,Gionfriddo M

    更新日期:1992-05-01 00:00:00

  • Advantages of Sirius Red staining for quantitative morphometric collagen measurements in lungs.

    abstract::Sirius Red staining is presented as a method for collagen determination, enabling quantitative morphometric measurements to be performed in locally defined tissue areas. The advantage of this method is especially shown for alveolar lung tissue. By excluding the bronchial areas in the tissue sections, the differences i...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902149509031745

    authors: Malkusch W,Rehn B,Bruch J

    更新日期:1995-01-01 00:00:00

  • Optimization of cationic liposome-mediated gene transfer to human bronchial epithelial cells expressing wild-type or abnormal cystic fibrosis transmembrane conductance regulator (CFTR).

    abstract::We determined optimum conditions for delivering DNA to transformed human bronchial epithelial cells expressing wild-type (BEAS) or abnormal (2CF) cystic fibrosis transmembrane conductance regulator (CFTR) using cationic liposomes (Lipofectin, [N-(N,N-dimethylaminoethane)carbamyl] cholesterol[DC-Chol]/dioleoylphosphati...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/019021499270259

    authors: Peters MT,Brigham KL,King GA,Meyrick BO,Gao X,Stecenko AA

    更新日期:1999-04-01 00:00:00

  • Effects of postnatal dexamethasone treatment on development of alveoli in adult rats.

    abstract::We compared the effects of dexamethasone given to rats from age 4 to 14 days, on alveolar development at age 99 days. Judged by similar nose-to-tail length and body weight, somatic growth was not altered by dexamethasone treatment. Lung volumes in both air- and saline-filled lungs and mean chord length (Lm) were incre...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148909069638

    authors: Sahebjami H,Domino M

    更新日期:1989-12-01 00:00:00

  • Antigen-induced bronchial hyperreactivity and bronchopulmonary inflammation in rats: effect of TNF receptor binding protein.

    abstract::The effect of a receptor binding protein for tumor necrosis factor (TNFrbp) on cell infiltration, bronchial hyperreactivity, and release of inflammatory mediators were studied following antigen challenge in sensitized rats. A 3-fold increase in total cell number, mainly neutrophils and eosinophils, was noted in bronch...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/019021401750069366

    authors: Carvalho CR,Jancar S,Conroy D,Sirois P

    更新日期:2001-03-01 00:00:00

  • Sex hormones influence growth and surfactant production in fetal lung explants.

    abstract::Sex-related differences may be present during fetal lung growth and at the onset of surfactant synthesis. In this study we investigated the role of dihydrotestosterone (DHT) and estrogen (EST) on cell division and on labeled palmitate incorporation into disaturated phosphatidylcholine (DSPC) at various times of gestat...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148909087851

    authors: McMillan EM,King GM,Adamson IY

    更新日期:1989-03-01 00:00:00

  • Long-term intermittent exposure to sulfuric acid aerosol, ozone, and their combination: alterations in tracheobronchial mucociliary clearance and epithelial secretory cells.

    abstract::Understanding the effects from long-term exposure to individual ambient air pollutants and mixtures of pollutants is necessary for adequate assessment of health risk. This study examined quantitative and temporal alterations in tracheobronchial mucociliary clearance function and bronchial epithelial secretory cells in...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902149209064343

    authors: Schlesinger RB,Gorczynski JE,Dennison J,Richards L,Kinney PL,Bosland MC

    更新日期:1992-07-01 00:00:00

  • Resveratrol ameliorates lung injury via inhibition of apoptosis in rats with severe acute pancreatitis.

    abstract::The objective of this study was to evaluate the protective effects of resveratrol on lung injury in rats with severe acute pancreatitis. Ninety-six male Sprague-Dawley rats were randomly classified into 4 equal groups (n = 24): control, model, resveratrol-treated, and dexamethasone-treated. The rats were evaluated at ...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/01902140902718197

    authors: Sha H,Ma Q,Jha RK,Wang Z

    更新日期:2009-05-01 00:00:00

  • Characterization of two protein-binding sites in the second intron of the mouse K-ras gene.

    abstract::A tandem repeat region in the second intron of the K-ras gene has been reported to be a possible regulatory site for transcription. In this study, a second protein-binding site was identified and characterized. It lies downstream (nucleotides 463 to 509) of the tandem repeat region. A T--> C base variation at nucleoti...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/0190214049049552

    authors: Chen B,Wang Y,You M

    更新日期:2005-03-01 00:00:00

  • Heme oxygenase-1 modulates thrombomodulin and activated protein C levels to attenuate lung injury in cecal ligation and puncture-induced acute lung injury mice.

    abstract::Acute lung injury (ALI) is often associated with sepsis and is the most common cause of acute respiratory failure. The authors evaluated the role of the heme oxygenase (HO)/carbon monoxide (CO) system on lung injury in a cecal ligation and puncture (CLP)-induced mouse model of ALI. The authors established CLP-induced ...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148.2012.660559

    authors: Fei D,Meng X,Kang K,Nan C,Zhao M,Pan S,Gao M,Yang S,Zhao M

    更新日期:2012-05-01 00:00:00

  • Two single nucleotide polymorphisms in TSLP gene are associated with asthma susceptibility in Chinese Han population.

    abstract:BACKGROUND:Asthma is a chronic inflammatory disease of the airway that is mediated by T-helper 2(TH2) cells. Thymic stromal lymphopoietin (TSLP) can aggravate asthmatic lung inflammation by activating dendritic cells (DCs) to promote TH2 differentiation. TSLP promoter polymorphisms are associated with susceptibility to...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148.2012.714840

    authors: Liu W,Xu LS,Liu QJ,Dong FZ,Qiu RF,Wen MC,Han YL,Tang NB,Kang LJ,Wu JX,Liu F,Zhao JP,Yang MM,Wang JF,Ding MJ,Sun YM,Fei WJ,Dong L

    更新日期:2012-10-01 00:00:00

  • Bombesin down modulates pulmonary fibrosis elicited in mice by bleomycin.

    abstract::The role of bombesin was investigated in the course of the pulmonary inflammation and fibrosis (PF) elicited by the intratracheal (IT) or intravenous (i.v.) administration of bleomycin in mice. Bleomycin-induced alveolitis was associated with an accumulation of cells, presumably macrophages, containing bombesin, as ev...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902149509068829

    authors: Piguet PF,Vesin C,Thomas F

    更新日期:1995-03-01 00:00:00

  • The sequential migration of neutrophils through endothelium and epithelium: a new model system.

    abstract::To better understand the mechanisms by which neutrophils migrate into the airways, we constructed a novel in vitro model system with human umbilical vein endothelial cell (HUVE) monolayers grown on top of permeable filters and human lung Type II-like alveolar epithelial cell (A549) monolayers grown on the undersurface...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902149809099591

    authors: Casale TB,Mower DA,Carolan EJ

    更新日期:1998-11-01 00:00:00

  • Calcium-dependent degradation of surfactant protein A by activated neutrophils due to serine proteases.

    abstract::The effects of activated leukocytes on surfactant function and composition were examined to better define the mechanisms by which acute inflammation contributes to respiratory distress syndrome (ARDS). Peripheral blood leukocytes from healthy volunteers were incubated in vitro with surfactant for 4 hours: (1) in the a...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/019021499270042

    authors: Schochett P,Mora R,Mark L,Butler M,Ingenito EP

    更新日期:1999-10-01 00:00:00

  • Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen.

    abstract::We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (99mTcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: co...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148709064313

    authors: Witten ML,Lemen RJ,Quan SF,Sobonya RE,Magarelli JL,Bruck DC

    更新日期:1987-01-01 00:00:00

  • Oral N-acetylcysteine speeds reversal of cigarette smoke-induced mucous cell hyperplasia in the rat.

    abstract::We set out to determine whether or not the "mucolytic" drug N-acetylcysteine would speed the reversal of cigarette smoke-induced secretory-cell hyperplasia to normal, similar to that found previously for two nonsteroidal antiinflammatory drugs. Cigarette smoke alone significantly (p less than 0.01) increased the numbe...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148809062848

    authors: Rogers DF,Godfrey RW,Majumdar S,Jeffery PK

    更新日期:1988-01-01 00:00:00

  • Assessment of the protective effect of amifostine on radiation-induced pulmonary toxicity.

    abstract::The objective of this study was to assess the radioprotective effects of amifostine in the rat model of radiation-induced lung injury using fractionated doses of radiation, to determine whether amifostine given before irradiation protects tumor from radiation cytotoxicity, and to determine whether changes in plasma le...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/01902140290096791

    authors: Vujaskovic Z,Feng QF,Rabbani ZN,Samulski TV,Anscher MS,Brizel DM

    更新日期:2002-10-01 00:00:00

  • Characteristic plethysmographic findings in a guinea pig model of COPD.

    abstract:AIM OF THE STUDY:Long-term exposure to cigarette smoke generates chronic obstructive pulmonary disease (COPD) in guinea pigs, but a comprehensive evaluation of changes in lung function, as assessed by barometric whole body plethysmography (WBP), is lacking. MATERIALS AND METHODS:Female guinea pigs were exposed to the ...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/01902148.2017.1294632

    authors: Ramírez-Ramírez E,Torres-Ramírez A,Alquicira-Mireles J,Cañavera-Constantino A,Segura-Medina P,Montaño-Ramírez M,Ramos-Abraham C,Vargas MH,Arreola-Ramírez JL

    更新日期:2017-03-01 00:00:00

  • Increased distension stimulates distal capillary growth as well as expression of specific angiogenesis genes in fetal mouse lungs.

    abstract::Tracheal occlusion (TO) performed surgically in utero near the end of gestation causes a rapid increase in the distension of future airspaces, resulting in accelerated lung development. The authors hypothesize that TO stimulates microvascular growth concomitant with a rapid increase in the expression of genes implicat...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/01902140701884331

    authors: Cloutier M,Maltais F,Piedboeuf B

    更新日期:2008-03-01 00:00:00

  • Tight junction alterations of respiratory epithelium following long-term NO2 exposure and recovery.

    abstract::Acute exposure to NO2 is reported to disrupt tight junctions in lung epithelium. We have studied the effects of chronic NO2 exposure and recovery breathing clean air to tight junctions of distal airway and alveolar epithelium. Syrian Golden hamsters were exposed to NO2 (30 PPM) for 5 or 9 months and a group of those a...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148609064295

    authors: Gordon RE,Solano D,Kleinerman J

    更新日期:1986-01-01 00:00:00

  • Role of endotoxin in tumor necrosis factor alpha expression from alveolar macrophages treated with urban air particles.

    abstract::The effects of urban air and diesel particles on inflammatory cytokine gene expression, tumor necrosis factor alpha (TNF-alpha) in particular, were studied in rat alveolar macrophages. TNF-alpha, interleukin (IL)-1, IL-6, cytokine-induced neutrophil chemoattractant (CINC), and macrophage inflammatory protein (MIP)-2 g...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902149609046043

    authors: Dong W,Lewtas J,Luster MI

    更新日期:1996-09-01 00:00:00

  • Expression and activity of matrix metallo proteinases 2 and 9 and their inhibitors in rat lungs during the perinatal period and in diaphragmatic hernia.

    abstract::During lung development, the extracellular matrix undergoes dynamic remodeling. Matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinases (TIMPs), are important enzymes that participate in regulating tissue remodeling. There is an abnormal balance of the synthesis and degradation of collagen...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.1080/01902140303783

    authors: Lemke RP,Zhang W,Balcerazak D,Kobayashi K,Schwingshackl A,Cheung PY,Dixon WT,Baracos VE,Greer JJ

    更新日期:2003-06-01 00:00:00

  • Effects of oxygen, calcium ionophore, and arachidonic acid on prostaglandin production by monolayer cultures of mixed cells and endothelial cells from rat fetal lungs.

    abstract::Prostaglandins (PGs) synthesized by fetal and neonatal lungs play pivotal roles in pulmonary physiology, especially during the transition from uterine to independent life. One regulator of prostaglandin synthesis at this time may be oxygen. We examined the effects of 1% O2, 21% O2 and 50% O2 in 5% CO2, balance N2 (PO2...

    journal_title:Experimental lung research

    pub_type: 杂志文章

    doi:10.3109/01902148709064301

    authors: Olson DM,Tanswell AK

    更新日期:1987-01-01 00:00:00