Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice.

Abstract:

:Interleukin-6 (IL-6) is known to be involved in the pathogenesis of various inflammatory diseases, but its role in bleomycin (BLM)-induced lung injury and subsequent fibrotic changes remains to be determined. We evaluated the role of IL-6 in the lung inflammatory changes induced by BLM using wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice. The mice were treated intratracheally with 1 mg/kg BLM and killed 2, 7, or 21 days later. Lung Inflammation in the acute phase (Days 2 and 7) was assessed by differential cell counts in bronchoalveolar lavage (BAL) fluid and cytokine levels in the lung. Lung fibrotic changes were evaluated on Day 21 by histopathology and collagen assay. On Day 2, BLM administration induced significant increases in the numbers of total cells, macrophages, and neutrophils in BAL fluid, which were attenuated in IL-6(-/-) mice (P < 0.05). Lung pathology also showed inflammatory cell accumulation, which was attenuated in the IL-6(-/-) mice compared with WT mice. In WT mice, elevated levels of TGF-beta(1) and CCL3 were observed 2 and 7 days after BLM challenge, respectively. On Day 7, BLM-induced inflammatory cell accumulation did not differ between the genotypes. Lung pathology 21 days after BLM challenge revealed significant fibrotic changes with increased collagen content, which was attenuated in IL-6(-/-) mice. Although the TGF-beta(1) level in the lung did not differ between the genotypes on Day 21, CCL3 was significantly lower in IL-6(-/-) mice. These results indicate that IL-6 may play an important role in the pathogenesis of BLM-induced lung injury and subsequent fibrotic changes.

authors

Saito F,Tasaka S,Inoue K,Miyamoto K,Nakano Y,Ogawa Y,Yamada W,Shiraishi Y,Hasegawa N,Fujishima S,Takano H,Ishizaka A

doi

10.1165/rcmb.2007-0299OC

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

566-71

issue

5

eissn

1044-1549

issn

1535-4989

pii

2007-0299OC

journal_volume

38

pub_type

杂志文章
  • Endothelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis.

    abstract::The pathological hallmark lesions in idiopathic pulmonary fibrosis are the fibroblastic foci, in which fibroblasts are thought to be involved in the tissue remodeling, matrix deposition, and cross-talk with alveolar epithelium. Recent evidence indicates that some fibroblasts in fibrosis may be derived from bone marrow...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0031OC

    authors: Hashimoto N,Phan SH,Imaizumi K,Matsuo M,Nakashima H,Kawabe T,Shimokata K,Hasegawa Y

    更新日期:2010-08-01 00:00:00

  • Identification of ras and ras-related low-molecular-mass GTP-binding proteins associated with rat lung lamellar bodies.

    abstract::Recent evidence from genetic experiments in yeast and from studies using guanosine triphosphate (GTP) analogues in mammalian cells suggests a key role for low-molecular-mass GTP-binding proteins (LMM-GBPs) (Mr 19 to 28 kD) in processes of intracellular vesicular sorting and secretion. Assembly and exocytosis of the la...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/6.3.253

    authors: Rubins JB,Panchenko M,Shannon TM,Dickey BF

    更新日期:1992-03-01 00:00:00

  • Anaphylatoxins Enhance Recruitment of Nonclassical Monocytes via Chemokines Produced by Pleural Mesothelial Cells in Tuberculous Pleural Effusion.

    abstract::In the present study, we sought to elucidate the mechanisms by which monocytes migrate into the pleural space in the presence of anaphylatoxins in tuberculous pleural effusion (TPE). Monocytes in both pleural effusion and blood were counted, and their phenotypic characteristics were analyzed. Activation of the complem...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2018-0075OC

    authors: Luo L,Li X,Hu X,Hu C,Tang W,Deng S,Feng J

    更新日期:2019-04-01 00:00:00

  • PKR regulates TLR2/TLR4-dependent signaling in murine alveolar macrophages.

    abstract::The double-stranded RNA (dsRNA)-activated serine/threonine kinase R (PKR) is well characterized as an essential component of the innate antiviral response. Recently, PKR has been implicated in Toll-like receptor (TLR) signal transduction in response to bacterial cell wall components. Its contribution to pulmonary immu...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0010OC

    authors: Cabanski M,Steinmüller M,Marsh LM,Surdziel E,Seeger W,Lohmeyer J

    更新日期:2008-01-01 00:00:00

  • Idiopathic pneumonia syndrome after allogeneic bone marrow transplantation in mice. Role of pretransplant radiation conditioning.

    abstract::Idiopathic pneumonia syndrome (IPS) is a significant clinical problem encountered among patients treated with bone marrow transplantation (BMT). IPS is identified as an inflammatory lung disease characterized by diffuse interstitial pneumonitis and alveolitis leading to interstitial fibrosis in the absence of an ident...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.20.6.3455

    authors: Shankar G,Scott Bryson J,Darrell Jennings C,Kaplan AM,Cohen DA

    更新日期:1999-06-01 00:00:00

  • Embryonic overexpression of receptors for advanced glycation end-products by alveolar epithelium induces an imbalance between proliferation and apoptosis.

    abstract::Receptors for advanced glycation end-products (RAGEs) are multiligand cell surface receptors highly expressed in the lung that contribute to alveolar epithelial cell differentiation during embryogenesis and the modulation of pulmonary inflammation during disease. When RAGEs are overexpressed throughout embryogenesis, ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2011-0385OC

    authors: Stogsdill JA,Stogsdill MP,Porter JL,Hancock JM,Robinson AB,Reynolds PR

    更新日期:2012-07-01 00:00:00

  • Genetic Deletion of β-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model.

    abstract::β-Arrestin-2 (βarr2) is a ubiquitously expressed cytosolic protein that terminates G protein-coupled receptor signaling and transduces G protein-independent signaling. We previously showed that mice lacking βarr2 do not develop an asthma phenotype when sensitized to, and challenged with, allergens. The current study e...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2014-0231OC

    authors: Chen M,Hegde A,Choi YH,Theriot BS,Premont RT,Chen W,Walker JK

    更新日期:2015-09-01 00:00:00

  • Notch induces myofibroblast differentiation of alveolar epithelial cells via transforming growth factor-{beta}-Smad3 pathway.

    abstract::Notch is an ancient cell-signaling system that regulates the specification of cell fate. This study examined the role of Notch in the epithelial-mesenchymal transition (EMT) and myofibroblast differentiation of cultured RLE-6TN cells (i.e., rat alveolar epithelial cells). The activation of Notch, either by ectopic exp...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0140oc

    authors: Aoyagi-Ikeda K,Maeno T,Matsui H,Ueno M,Hara K,Aoki Y,Aoki F,Shimizu T,Doi H,Kawai-Kowase K,Iso T,Suga T,Arai M,Kurabayashi M

    更新日期:2011-07-01 00:00:00

  • Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway.

    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

    authors: Meng Y,Yu CH,Li W,Li T,Luo W,Huang S,Wu PS,Cai SX,Li X

    更新日期:2014-04-01 00:00:00

  • The Transient Receptor Potential Channel Vanilloid 1 Is Critical in Innate Airway Epithelial Responses to Protease Allergens.

    abstract::The airway epithelium plays a critical role in innate responses to airborne allergens by secreting IL-1 family cytokines such as IL-1α and IL-33 as alarmins that subsequently orchestrate appropriate immune responses. Previous studies revealed that epithelial IL-33 secretion by allergens such as Alternaria alternata or...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2019-0170OC

    authors: Schiffers C,Hristova M,Habibovic A,Dustin CM,Danyal K,Reynaert NL,Wouters EFM,van der Vliet A

    更新日期:2020-08-01 00:00:00

  • Development of lentiviral vectors with regulated respiratory epithelial expression in vivo.

    abstract::Development of gene transfer vectors with regulated, lung-specific expression will be a useful tool for studying lung biology and developing gene therapies. In this study we constructed a series of lentiviral vectors with regulatory elements predicted to produce lung-specific transgene expression: the surfactant prote...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2006-0276OC

    authors: Hendrickson B,Senadheera D,Mishra S,Bui KC,Wang X,Chan B,Petersen D,Pepper K,Lutzko C

    更新日期:2007-10-01 00:00:00

  • Fluticasone propionate attenuates ozone-induced rhinitis and mucous cell metaplasia in rat nasal airway epithelium.

    abstract::Ozone (O3) is the principal oxidant pollutant in photochemical smog. Repeated exposures to O3 induces inflammation and mucous cell metaplasia in the nasal airways of laboratory animals. Our study was designed to determine the efficacy of a topical anti-inflammatory corticosteroid in preventing O3-induced rhinitis and ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.18.1.2897

    authors: Hotchkiss JA,Hilaski R,Cho H,Regan K,Spencer P,Slack K,Harkema JR

    更新日期:1998-01-01 00:00:00

  • Biased TAS2R Bronchodilators Inhibit Airway Smooth Muscle Growth by Downregulating Phosphorylated Extracellular Signal-regulated Kinase 1/2.

    abstract::Bitter taste receptor (TAS2R) agonists dilate airways by receptor-dependent smooth muscle relaxation. Besides their coupling to relaxation, we have found that human airway smooth muscle (HASM) cell TAS2Rs activate (phosphorylate) extracellular signal-related kinase 1/2 (ERK1/2), but the cellular effects are not known....

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2018-0189OC

    authors: Kim D,Cho S,Castaño MA,Panettieri RA,Woo JA,Liggett SB

    更新日期:2019-05-01 00:00:00

  • Hepatocyte growth factor inhibits epithelial to myofibroblast transition in lung cells via Smad7.

    abstract::Idiopathic pulmonary fibrosis is a lethal parenchymal lung disease characterized by denudation of the lung epithelium, fibroblast proliferation, and collagen deposition. Cellular changes underlying disease progression involve injury to alveolar epithelial cells, epithelial to mesenchymal transition, proliferation of a...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2008-0217OC

    authors: Shukla MN,Rose JL,Ray R,Lathrop KL,Ray A,Ray P

    更新日期:2009-06-01 00:00:00

  • Neutrophil-Expressed p21/waf1 Favors Inflammation Resolution in Pseudomonas aeruginosa Infection.

    abstract::Neutrophil-associated inflammation during Pseudomonas aeruginosa lung infection is a determinant of morbidity in cystic fibrosis (CF). Neutrophil apoptosis is a key factor in inflammation resolution and is controlled by cytosolic proliferating cell nuclear antigen (PCNA). p21/Waf1, a cyclin-dependent kinase inhibitor,...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2015-0047OC

    authors: Martin C,Ohayon D,Alkan M,Mocek J,Pederzoli-Ribeil M,Candalh C,Thevenot G,Millet A,Tamassia N,Cassatella MA,Thieblemont N,Burgel PR,Witko-Sarsat V

    更新日期:2016-05-01 00:00:00

  • The matrix metalloproteinases and their inhibitors.

    abstract::A number of metalloproteinases that degrade the extracellular matrix of connective tissues and two specific tissue inhibitors of metalloproteinases (TIMPs) have now been isolated, characterized, and cloned. Comparison of the enzyme sequences has allowed the delineation of domain structures, and initial studies have be...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/ajrcmb/7.2.120

    authors: Murphy G,Docherty AJ

    更新日期:1992-08-01 00:00:00

  • High Mobility Group Box-1 mediates hyperoxia-induced impairment of Pseudomonas aeruginosa clearance and inflammatory lung injury in mice.

    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

    authors: Patel VS,Sitapara RA,Gore A,Phan B,Sharma L,Sampat V,Li JH,Yang H,Chavan SS,Wang H,Tracey KJ,Mantell LL

    更新日期:2013-03-01 00:00:00

  • Effect of neutrophil mediators on epithelial permeability.

    abstract::Inflammatory lung disease is associated with increased epithelial permeability, but it is unclear how inflammatory cells alter epithelial permeability. Neutrophils have azurophilic granules containing elastase, cathepsin G, and defensins which are released at sites of inflammation. Experiments using whole animals and ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.13.6.7576710

    authors: Peterson MW,Walter ME,Nygaard SD

    更新日期:1995-12-01 00:00:00

  • Lung-specific expression of dominant-negative mutant p53 in transgenic mice increases spontaneous and benzo(a)pyrene-induced lung cancer.

    abstract::Mutations in the p53 gene have been implicated to play an important role in the development of various human cancers. To evaluate the importance of p53 in lung cancer, a transgenic mouse model was established by utilizing the Clara cell secretory protein (CCSP) promoter to target the expression of a dominant-negative ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.27.2.4799

    authors: Tchou-Wong KM,Jiang Y,Yee H,LaRosa J,Lee TC,Pellicer A,Jagirdar J,Gordon T,Goldberg JD,Rom WN

    更新日期:2002-08-01 00:00:00

  • Dissection of the hyperadhesive phenotype of airway eosinophils in asthma.

    abstract::Asthma is characterized by appearance of eosinophils in the airway. Eosinophils purified from the airway 48 h after segmental antigen challenge are described as exhibiting greater adhesion to albumin-coated surfaces via an unidentified beta2 integrin and increased expression of alphaMbeta2 (CD11b/18) compared with pur...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2006-0027OC

    authors: Barthel SR,Jarjour NN,Mosher DF,Johansson MW

    更新日期:2006-09-01 00:00:00

  • Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway.

    abstract::Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Cisplatin remains the main drug for treating advanced non-small-cell lung cancer. However, drug r...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2012-0244OC

    authors: Lin CC,Yeh HH,Huang WL,Yan JJ,Lai WW,Su WP,Chen HH,Su WC

    更新日期:2013-08-01 00:00:00

  • Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase.

    abstract::The expression of bombesin-like peptides (BLPs) by pulmonary neuroendocrine cells is transiently upregulated during lung development. A functional role for BLPs is supported by their ability to stimulate lung growth and maturation both in vitro and in vivo during the late stages of lung development. In addition, the c...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.10.6.8003340

    authors: Aguayo SM,Schuyler WE,Murtagh JJ Jr,Roman J

    更新日期:1994-06-01 00:00:00

  • Monkey Clara cell 10 kDa protein (CC10): a characterization of the amino acid sequence with an evolutional comparison with humans, rabbits, rats, and mice.

    abstract::Monkey Clara cell 10 kDa protein (CC10) was purified from monkey lung lavage. This protein showed an apparent molecular weight of about 10 kDa and 5 kDa under non-reducing and reducing conditions, respectively, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. From the amino acid sequence dat...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.15.3.8810640

    authors: Hashimoto S,Nakagawa K,Sueishi K

    更新日期:1996-09-01 00:00:00

  • Hemorrhagic shock activates lung endothelial reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase via neutrophil NADPH oxidase.

    abstract::The vascular endothelium plays an important role in the regulation of inflammatory responses after trauma and hemorrhage. Interactions of neutrophils with endothelial cells (ECs) contribute to the activation of specific EC responses involved in innate immunity. We have previously reported that oxidants derived from th...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0408OC

    authors: Xiang M,Yin L,Li Y,Xiao G,Vodovotz Y,Billiar TR,Wilson MA,Fan J

    更新日期:2011-03-01 00:00:00

  • The antimicrobial/elastase inhibitor elafin regulates lung dendritic cells and adaptive immunity.

    abstract::Infections with bacteria and viruses such as adenovirus are a feature of chronic lung diseases such as chronic obstructive pulmonary diseases (COPD), and may be instrumental in the generation of disease exacerbations. We have previously shown in acute models that elafin (a lung natural chemotactic molecule for macroph...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2005-0405OC

    authors: Roghanian A,Williams SE,Sheldrake TA,Brown TI,Oberheim K,Xing Z,Howie SE,Sallenave JM

    更新日期:2006-05-01 00:00:00

  • Regulation of hydrogen peroxide generation in cultured endothelial cells.

    abstract::Endogenous hydrogen peroxide (H2O2) release from aortic endothelial cells was studied in the presence of antioxidant enzyme inhibitors, mitochondrial inhibitors, a microsomal cytochrome P-450 inhibitor, and after oxidative stress induced with H2O2 or menadione. Extracellular H2O2 generation was determined spectrofluor...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/6.2.175

    authors: Kinnula VL,Whorton AR,Chang LY,Crapo JD

    更新日期:1992-02-01 00:00:00

  • Transforming growth factor-beta increases elastin production by neonatal rat lung fibroblasts.

    abstract::While elastin degradation is a hallmark of pulmonary emphysema, it is likely that elastin synthesis also occurs. However, the supramolecular structure and function of the newly synthesized elastin are abnormal. Very little is known about the regulation of elastin synthesis during the development of emphysema when prom...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/3.4.369

    authors: McGowan SE,McNamer R

    更新日期:1990-10-01 00:00:00

  • Platelet-activating factor-induced human eosinophil transendothelial migration: evidence for a dynamic role of the endothelium.

    abstract::Stimulated migration of eosinophils out of the bloodstream and into the lung is key in the development of tissue eosinophilia and inflammation in asthma. Platelet-activating factor (PAF) has been implicated as an important inflammatory mediator in asthma pathogenesis in part because of its chemotactic capacity. We the...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/8.1.77

    authors: Casale TB,Erger RA,Little MM

    更新日期:1993-01-01 00:00:00

  • Cyclooxygenase-2 and microRNA-155 expression are elevated in asthmatic airway smooth muscle cells.

    abstract::Cyclooxygenase-2 (COX-2) expression and PGE2 secretion from human airway smooth muscle cells (hASMCs) may contribute to β2-adrenoceptor hyporesponsiveness, a clinical feature observed in some patients with asthma. hASMCs from patients with asthma exhibit elevated expression of cytokine-responsive genes, and in some in...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2014-0129OC

    authors: Comer BS,Camoretti-Mercado B,Kogut PC,Halayko AJ,Solway J,Gerthoffer WT

    更新日期:2015-04-01 00:00:00

  • Cytokines induce an early steroid resistance in airway smooth muscle cells: novel role of interferon regulatory factor-1.

    abstract::We have previously shown that long-term treatment of airway smooth muscle (ASM) cells with a combination of TNF-alpha and IFN-gamma impaired steroid anti-inflammatory action through the up-regulation of glucocorticoid receptor beta isoform (GRbeta) (Mol Pharmacol 2006;69:588-596). We here found that steroid actions co...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2007-0226OC

    authors: Tliba O,Damera G,Banerjee A,Gu S,Baidouri H,Keslacy S,Amrani Y

    更新日期:2008-04-01 00:00:00