Targeting the MEK1 cascade in lung epithelium inhibits proliferation and fibrogenesis by asbestos.

Abstract:

:The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are phosphorylated after inhalation of asbestos. The effect of blocking this signaling pathway in lung epithelium is unclear. Asbestos-exposed transgenic mice expressing a dominant-negative mitogen-activated protein kinase kinase-1 (dnMEK1) (i.e., the upstream kinase necessary for phosphorylation of ERK1/2) targeted to lung epithelium exhibited morphologic and molecular changes in lung. Transgene-positive (Tg+) (i.e., dnMEK1) and transgene-negative (Tg-) littermates were exposed to crocidolite asbestos for 2, 4, 9, and 32 days or maintained in clean air (sham controls). Distal bronchiolar epithelium was isolated using laser capture microdissection and mRNA analyzed for molecular markers of proliferation and Clara cell secretory protein (CCSP). Lungs and bronchoalveolar lavage fluids were analyzed for inflammatory and proliferative changes and molecular markers of fibrogenesis. Distal bronchiolar epithelium of asbestos-exposed wild-type mice showed increased expression of c-fos at 2 days. Elevated mRNA levels of histone H3 and numbers of Ki-67-labeled proliferating bronchiolar epithelial cells were decreased at 4 days in asbestos-exposed Tg+ mice. At 32 days, distal bronchioles normally composed of Clara cells in asbestos-exposed Tg+ mouse lungs exhibited nonreplicating ciliated and mucin-secreting cells as well as decreased mRNA levels of CCSP. Gene expression (procollagen 3-a-1, procollagen 1-a-1, and IL-6) linked to fibrogenesis was also increased in lung homogenates of asbestos-exposed Tg- mice, but reduced in asbestos-exposed Tg+ mice. These results suggest a critical role of MEK1 signaling in epithelial cell proliferation and lung remodeling after toxic injury.

authors

Manning CB,Sabo-Attwood T,Robledo RF,Macpherson MB,Rincón M,Vacek P,Hemenway D,Taatjes DJ,Lee PJ,Mossman BT

doi

10.1165/rcmb.2007-0382OC

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

618-26

issue

5

eissn

1044-1549

issn

1535-4989

pii

2007-0382OC

journal_volume

38

pub_type

杂志文章
  • 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

  • Elevated levels of the IGF-binding protein protease MMP-1 in asthmatic airway smooth muscle.

    abstract::We have previously demonstrated that the asthma-associated proinflammatory eicosanoid leukotriene D4 (LTD4) is co-mitogenic with insulin-like growth factors (IGFs) in airway smooth-muscle (ASM) cells in vitro. This synergistic effect of LTD4 and IGF on ASM cell growth involves proteolysis of ASM-produced IGF binding p...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.20.2.3148

    authors: Rajah R,Nachajon RV,Collins MH,Hakonarson H,Grunstein MM,Cohen P

    更新日期:1999-02-01 00:00:00

  • IL-12 and IFN-gamma are required for initiating the protective Th1 response to pulmonary cryptococcosis in resistant C.B-17 mice.

    abstract::A murine model was used to assess the role of cytokines in initiating protective T-cell-mediated immunity in the lung. A pulmonary infection was initiated by intratracheal inoculation of Cryptococcus neoformans (Cne). Previously, we had established that Cne lung clearance was mouse-strain-specific: C.B-17 mice were re...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.17.6.2879

    authors: Hoag KA,Lipscomb MF,Izzo AA,Street NE

    更新日期:1997-12-01 00:00:00

  • Differential regulation of the genes encoding platelet-derived growth factor receptor and its ligand in rat lung during microvascular and alveolar wall remodeling in hyperoxia.

    abstract::The growth factors that operate while the lung remodels in hyperoxia are not known. At the lung periphery, high oxygen levels cause cell hypertrophy and hyperplasia, and this results in a thickening of the alveolar-capillary membrane and the walls of its associated microvessels. The present study examines gene express...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/7.3.278

    authors: Powell PP,Wang CC,Jones R

    更新日期:1992-09-01 00:00:00

  • Hypersensitivity pneumonitis: whole Micropolyspora faeni or antigens thereof stimulate the release of proinflammatory cytokines from macrophages.

    abstract::Hypersensitivity pneumonitis (HP) is an allergic granulomatous interstitial lung disease resulting from a reaction of selected individuals to repeated inhalations of certain antigens. HP is characterized by chronic inflammation, and the development of the disease seems to be immunologically mediated. In farmer's lung,...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/5.2.198

    authors: Denis M,Cormier Y,Tardif J,Ghadirian E,Laviolette M

    更新日期:1991-08-01 00:00:00

  • Proteolytic cleavage of fibrinogen: amplification of its surfactant inhibitory capacity.

    abstract::Severe deterioration of surfactant function is noted under conditions of plasma protein leakage into the alveolar space; moreover, fibrinogen has previously been reported to possess strong surfactant inhibitory capacity. Dissolution of alveolar deposits of fibrinogen and fibrin (e.g., hyaline membranes) requires enzym...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/9.3.239

    authors: Seeger W,Grube C,Günther A

    更新日期:1993-09-01 00:00:00

  • Clarithromycin inhibits interleukin-13-induced goblet cell hyperplasia in human airway cells.

    abstract::IL-13 is a T-helper class 2 cytokine that induces goblet cell hyperplasia and mucus production in airway epithelial cells. Because macrolide antibiotics are known to have immunomodulatory and mucoregulatory properties, the aim of this study was to examine the effect of clarithromycin on IL-13-induced goblet cell hyper...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0327OC

    authors: Tanabe T,Kanoh S,Tsushima K,Yamazaki Y,Kubo K,Rubin BK

    更新日期:2011-11-01 00:00:00

  • Pluripotent allospecific CD8+ effector T cells traffic to lung in murine obliterative airway disease.

    abstract::Long-term success in lung transplantation is limited by obliterative bronchiolitis, whereas T cell effector mechanisms in this process remain incompletely understood. Using the mouse heterotopic allogeneic airway transplant model, we studied T cell effector responses during obliterative airways disease (OAD). Allospec...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2005-0164OC

    authors: West EE,Lavoie TL,Orens JB,Chen ES,Ye SQ,Finkelman FD,Garcia JG,McDyer JF

    更新日期:2006-01-01 00:00:00

  • Enhanced expression of GM-CSF in differentiating eosinophils of atopic and atopic asthmatic subjects.

    abstract::Higher numbers of eosinophil/basophil colony-forming units (Eo/B CFU) are observed in blood of atopic individuals, and can be enhanced in atopic asthmatics by allergen-inhalation challenge. It is known that mature basophils and eosinophils synthesize cytokines relevant to allergic inflammation. To investigate the pote...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.19.1.2871

    authors: Gauvreau GM,O'Byrne PM,Moqbel R,Velazquez J,Watson RM,Howie KJ,Denburg JA

    更新日期:1998-07-01 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

  • Modulators of sphingolipid metabolism reduce lung inflammation.

    abstract::The investigation of novel targets for the treatment of cystic fibrosis (CF) lung inflammation is a major priority, considering that no effective therapy is available for this purpose. Consistent with the evidence that the sphingolipid (SL) ceramide regulates airway inflammation and infection in mice and patients with...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0457OC

    authors: Dechecchi MC,Nicolis E,Mazzi P,Cioffi F,Bezzerri V,Lampronti I,Huang S,Wiszniewski L,Gambari R,Scupoli MT,Berton G,Cabrini G

    更新日期:2011-10-01 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

  • Early regulatory changes in rat pulmonary artery of renin-dependent systemic hypertension models.

    abstract::Patients with systemic hypertension of various etiologies maintain their pulmonary artery pressures within normal limits. We have reported in isolated perfused rat lungs that low basal tone appears to be regulated by nitric oxide (NO)-dependent and -independent mechanisms of soluble guanylate cyclase activation, and s...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.15.4.8879180

    authors: Itani MM,Talerico MG,Pino PA,Burke-Wolin T

    更新日期:1996-10-01 00:00:00

  • Influenza induces endoplasmic reticulum stress, caspase-12-dependent apoptosis, and c-Jun N-terminal kinase-mediated transforming growth factor-β release in lung epithelial cells.

    abstract::Influenza A virus (IAV) infection is known to induce endoplasmic reticulum (ER) stress, Fas-dependent apoptosis, and TGF-β production in a variety of cells. However, the relationship between these events in murine primary tracheal epithelial cells (MTECS), which are considered one of the primary sites of IAV infection...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2010-0460OC

    authors: Roberson EC,Tully JE,Guala AS,Reiss JN,Godburn KE,Pociask DA,Alcorn JF,Riches DW,Dienz O,Janssen-Heininger YM,Anathy V

    更新日期:2012-05-01 00:00:00

  • Inhaled asbestos fibers induce p53 expression in the rat lung.

    abstract::Humans and rodents exposed to an aerosol of asbestos fibers develop lung injury that can lead to a fibroproliferative response culminating in excessive scarring and impaired lung function. To define the early events that precede asbestos-induced fibrotic lung disease, rats were exposed to an aerosol of chrysotile asbe...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.16.4.9115760

    authors: Mishra A,Liu JY,Brody AR,Morris GF

    更新日期:1997-04-01 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

  • Fibroblast tropoelastin and alpha-smooth-muscle actin expression are repressed by particulate-activated macrophage-derived tumor necrosis factor-alpha in experimental silicosis.

    abstract::Lung elastin synthesis is normally confined to periods of development, is maximal during alveolarization, and declines to low levels in mature lung. We have previously described an elastogenic response in the adult rat lung associated with experimental granulomatous disease induced by silica instillation. Reinitiated ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.21.2.3641

    authors: Mariani TJ,Arikan MC,Pierce RA

    更新日期:1999-08-01 00:00:00

  • Adenovirus E1A 13S gene product up-regulates the cytomegalovirus major immediate early promoter.

    abstract::Latent cytomegalovirus (CMV) infection is often reactivated in the lung. We postulated that this reactivation could occur by stimulation of the CMV major immediate early (IE) promoter by other viruses that infect the lung. The specific aim of this study was to investigate whether adenovirus early proteins could stimul...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.10.4.8136160

    authors: Metcalf JP,Monick MM,Stinski MF,Hunninghake GW

    更新日期:1994-04-01 00:00:00

  • Effect of IgA on respiratory burst and cytokine release by human alveolar macrophages: role of ERK1/2 mitogen-activated protein kinases and NF-kappaB.

    abstract::Human alveolar macrophages (HAM) express FcalphaR receptors for immunoglobulin (Ig)A which could link humoral and cellular branches of lung immunity. Here, we investigate the effects of polymeric (p-IgA) and secretory (S-IgA) IgA interaction with Fc(alpha)R on lipopolysaccharide (LPS)- and phorbol myristate acetate (P...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.26.3.4590

    authors: Ouadrhiri Y,Pilette C,Monteiro RC,Vaerman JP,Sibille Y

    更新日期:2002-03-01 00:00:00

  • Activation of murine macrophages by silica particles in vitro is a process independent of silica-induced cell death.

    abstract::We have tested the murine macrophagic cell line RAW 264.7 for its ability to undergo activation after exposure to silica particles in vitro. When exposed to silica under controlled conditions (each cell having access to about 10 silica particles), RAW 264.7 cells were able to phagocytose the particles. Concomitantly, ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.13.5.7576690

    authors: Claudio E,Segade F,Wróbel K,Ramos S,Lazo PS

    更新日期:1995-11-01 00:00:00

  • Reversible or irreversible remodeling in pulmonary arterial hypertension.

    abstract::Vascular remodeling is an important pathological feature of pulmonary arterial hypertension (PAH), which leads to increased pulmonary vascular resistance, with marked proliferation of pulmonary artery smooth muscle cells (SMC) and/or endothelial cells (EC). Successful treatment of experimental PAH with a platelet-deri...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2009-0389TR

    authors: Sakao S,Tatsumi K,Voelkel NF

    更新日期:2010-12-01 00:00:00

  • Mechanisms of interferon-γ production by neutrophils and its function during Streptococcus pneumoniae pneumonia.

    abstract::Bacterial pneumonia is a common public health problem associated with significant mortality, morbidity, and cost. Neutrophils are usually the earliest leukocytes to respond to bacteria in the lungs. Neutrophils rapidly sequester in the pulmonary microvasculature and migrate into the lung parenchyma and alveolar spaces...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0316OC

    authors: Gomez JC,Yamada M,Martin JR,Dang H,Brickey WJ,Bergmeier W,Dinauer MC,Doerschuk CM

    更新日期:2015-03-01 00:00:00

  • Expression and biological activity of ABCA1 in alveolar epithelial cells.

    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

    authors: Bates SR,Tao JQ,Yu KJ,Borok Z,Crandall ED,Collins HL,Rothblat GH

    更新日期:2008-03-01 00:00:00

  • Histamine inhibits tumor necrosis factor alpha release by mast cells through H2 and H3 receptors.

    abstract::Histamine was one of the first inflammatory mediators thought to be important in the pathophysiology of asthma, but it is not now thought to be a mediator with primary importance in airway constriction. However, histamine has several effects that may be relevant. One of these effects, its immunoregulatory role, has be...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.14.6.8652190

    authors: Bissonnette EY

    更新日期:1996-06-01 00:00:00

  • Autocrine ligands for the epidermal growth factor receptor mediate interleukin-8 release from bronchial epithelial cells in response to cigarette smoke.

    abstract::Airway neutrophilia is a prominent feature of chronic obstructive pulmonary disease. As cigarette smoke (CS) and epidermal growth factor (EGF) both cause release of interleukin-8 (IL-8) from epithelial cells in vitro, we investigated whether autocrine ligands for the EGF receptor (EGFR) are involved in this proinflamm...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.27.1.4789

    authors: Richter A,O'Donnell RA,Powell RM,Sanders MW,Holgate ST,Djukanović R,Davies DE

    更新日期:2002-07-01 00:00:00

  • NOX1 Promotes Mesothelial-Mesenchymal Transition Through Modulation of ROS-mediated Signaling.

    abstract::Pleural organization may occur after empyema or complicated parapneumonic effusion and can result in restrictive lung disease with pleural fibrosis (PF). Pleural mesothelial cells; PMCs, may contribute to PF through acquisition of a profibrotic phenotype; meso-mesenchymal transition (MesoMT), which is characterized by...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2020-0077OC

    authors: Qin W,Jeffers A,Owens S,Chauhan P,Komatsu S,Qian G,Guo X,Ikebe M,Idell S,Tucker TA

    更新日期:2021-01-29 00:00:00

  • Senescence-associated secretory phenotype and its possible role in chronic obstructive pulmonary disease.

    abstract::Chronic obstructive pulmonary disease (COPD) is a major disease of the lungs. It primarily occurs after a prolonged period of cigarette smoking. Chronic inflammation of airways and the alveolar space as well as lung tissue destruction are the hallmarks of COPD. Recently it has been shown that cellular senescence might...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2013-0382PS

    authors: Kumar M,Seeger W,Voswinckel R

    更新日期:2014-09-01 00:00:00

  • Endothelin-1 inhibits background two-pore domain channel TASK-1 in primary human pulmonary artery smooth muscle cells.

    abstract::Endothelin (ET)-1 causes long-lasting vasoconstriction and vascular remodeling by interacting with specific G-protein-coupled receptors in pulmonary artery smooth muscle cells (PASMCs), and thus plays an important role in the pathophysiology of pulmonary arterial hypertension. The two-pore domain K(+) channel, TASK-1,...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2008-0412OC

    authors: Tang B,Li Y,Nagaraj C,Morty RE,Gabor S,Stacher E,Voswinckel R,Weissmann N,Leithner K,Olschewski H,Olschewski A

    更新日期:2009-10-01 00:00:00

  • Fetal alveolar epithelial cells contain [D-Ala(2)]-deltorphin I-like immunoreactivity: delta- and mu-opiate receptors mediate opposite effects in developing lung.

    abstract::Opiate-like peptides can regulate many cellular functions. We now map [D-Ala(2)]deltorphin I (DADTI)-like immunoreactivity (DADTI-LI) in developing mouse lung and analyze potential functional roles. Most DADTI-LI-positive cells were alveolar cells negative for prosurfactant protein (proSP)-C immunoreactivity. Peak num...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.25.4.4072

    authors: Sunday ME,Haley KJ,Emanuel RL,Torday JS,Asokananthan N,Sikorski KA,Tooyama I,Kimura H,Renda T,Erspamer V

    更新日期:2001-10-01 00:00:00

  • Pathways of fibrin turnover of human pleural mesothelial cells in vitro.

    abstract::The mesothelium contains both procoagulant and fibrinolytic activities. An imbalance between these activities could account for the abnormal fibrin turnover and pleural fibrin deposition that is characteristic of pleural inflammation. Procoagulant activity of human pleural mesothelial cells (HPMC) is in part due to ti...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/7.4.414

    authors: Idell S,Zwieb C,Kumar A,Koenig KB,Johnson AR

    更新日期:1992-10-01 00:00:00