Abstract:
:High mobility group box 1 (HMGB1) is an alarmin released from macrophages after infection or inflammation and is a biomarker of lung disease progression in patients with cystic fibrosis. We reported that 2-O, 3-O desulfated heparin (ODSH) inhibits the release of HMGB1 from murine macrophages triggered by neutrophil elastase both in vivo and in vitro. HMGB1 shuttles between the nucleus and the cytoplasm. When acetylated at lysine residues in the nuclear localization signal domains, HMGB1 is sequestered in the cytoplasm and is fated for secretion. In this study, we investigated the mechanism by which ODSH blocks HMGB1 secretion. We tested whether ODSH inhibits the activity of p300, a histone acetyltransferase that has been linked to HMGB1 acetylation and release. ODSH inhibited both neutrophil elastase and LPS-triggered HMGB1 release from the murine macrophage cell line RAW264.7 in a concentration-dependent manner. Fluorescein-labeled ODSH was taken up by RAW264.7 cells into the cytoplasm as well as the nucleus, suggesting an intracellular site of action of ODSH for blocking HMGB1 release. ODSH inhibited RAW264.7 cell nuclear extract, human macrophage nuclear extract, and recombinant p300 HAT activity in vitro, resulting in the failure to acetylate HMGB1. In silico molecular modeling predicted that of the numerous possible ODSH sequences, a small number preferentially recognizes a specific binding site on p300. Fluorescence binding studies showed that ODSH bound p300 tightly (dissociation constant ∼1 nM) in a highly cooperative manner. These results suggest that ODSH inhibited HMGB1 release, at least in part, by direct molecular inhibition of p300 HAT activity.
journal_name
Am J Respir Cell Mol Biolauthors
Zheng S,Kummarapurugu AB,Afosah DK,Sankaranarayanan NV,Boothello RS,Desai UR,Kennedy T,Voynow JAdoi
10.1165/rcmb.2016-0069OCsubject
Has Abstractpub_date
2017-01-01 00:00:00pages
90-98issue
1eissn
1044-1549issn
1535-4989journal_volume
56pub_type
杂志文章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
更新日期:2009-06-01 00:00:00
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
更新日期:1992-03-01 00:00:00
abstract::Hyperplasia of airway smooth muscle cells is present in the airways of asthmatic patients and may contribute to the development of the bronchial hyperresponsiveness that occurs in these patients. Because tryptase is an abundant component of mast cell granules and has demonstrated growth-stimulatory effects in other me...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.13.2.7626290
更新日期:1995-08-01 00:00:00
abstract::Clara cell secretory protein (CCSP), or CC10, is an inhibitor of secretory phospholipase A2 which may be produced by phagocytic cells and by a variety of other cells in the airway. Tumor necrosis factor-alpha (TNF-alpha) is capable of activating phospholipases and inducing the expression of a variety of genes in the a...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.19.4.3129
更新日期:1998-10-01 00:00:00
abstract::Cystic fibrosis (CF) is a lethal genetic disease characterized by progressive lung damage and airway obstruction. The majority of patients demonstrate airway hyperresponsiveness (AHR), which is associated with more rapid lung function decline. Recent studies in the neonatal CF pig demonstrated airway smooth muscle (AS...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2019-0158OC
更新日期:2020-05-01 00:00:00
abstract::We hypothesized that, as in animal models, localized deposition of antigen into the human lung would induce local inflammatory and immune responses in antigen-exposed sites. To test this hypothesis, segmental instillation of a well-characterized, highly immunogenic, soluble antigen, keyhole limpet hemocyanin (KLH) was...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.11.5.7946390
更新日期:1994-11-01 00:00:00
abstract::The etiology of acute lung injury is complex and associated with numerous, chemically diverse precipitating factors. During acute lung injury in mice, one key event is epithelial cell injury that leads to reduced surfactant biosynthesis. We have previously reported that transgenic mice that express transforming growth...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0317OC
更新日期:2009-08-01 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) is a cytokine implicated in wound healing and in the pathogenesis of pulmonary fibrosis. TGF-beta stimulates myofibroblast differentiation characterized by expression of contractile smooth muscle (SM)-specific proteins such as SM-alpha-actin. In the present study, we examined...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0288OC
更新日期:2009-09-01 00:00:00
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
更新日期:1994-04-01 00:00:00
abstract::The dynamics and mechanisms of extracellular release of hydrogen peroxide (H2O2) from bovine pulmonary artery endothelial cells (EC) subjected to anoxia, hypoxia, and hypoxia followed by reoxygenation were examined using various inhibitors of enzymatic systems in intact cells and by direct measurement of H2O2 producti...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.12.1.7529030
更新日期:1995-01-01 00:00:00
abstract::Tissue inhibitor of metalloproteinases-3 (TIMP-3) has emerged as a key mediator of inflammation. Recently, we reported that the resolution of inflammation is impaired in Timp3(-/-) mice after bleomycin-induced lung injury. Here, we demonstrate that after LPS instillation (another model of acute lung injury), Timp3(-/-...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2012-0377OC
更新日期:2013-11-01 00:00:00
abstract::We have previously observed that mice exposed to cigarette smoke and treated with exogenous alpha(1)-antitrypsin (A1AT) were protected against the development of emphysema and against smoke-induced increases in serum TNF-alpha. To investigate possible mechanisms behind this latter observation, we cultured alveolar mac...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2006-0345OC
更新日期:2007-08-01 00:00:00
abstract::Pneumocystis carinii causes severe pneumonia in immunocompromised patients. Recent studies indicate that P. carinii uses a Cdc2 cyclin-dependent kinase to control its proliferation. To further study the regulation of the life cycle of P. carinii, we characterized the P. carinii B-type cyclin termed Cdc13, whose bindin...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.22.6.3838
更新日期:2000-06-01 00:00:00
abstract::The time course and nature of the cellular response to left pneumonectomy, with or without prior adrenalectomy, were evaluated in the right lungs of male Sprague-Dawley rats using morphometric techniques. Animals were studied at days 2, 5, and 14 following pneumonectomy, intervals prior to, during the course of, and f...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/5.4.351
更新日期:1991-10-01 00:00:00
abstract::In allergic airway diseases, intermediate progenitor cells (IPCs) increase in number in the surface epithelium. IPCs arise from basal cells, the origin of hallmark pathological changes, including goblet cell hyperplasia and mucus hypersecretion. Thus, targeting IPCs will benefit future treatment of allergic airway dis...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2020-0350OC
更新日期:2020-12-02 00:00:00
abstract::Vitamin A deficiency strongly predicts the risk of developing tuberculosis (TB) in individuals exposed to Mycobacterium tuberculosis (Mtb). The burden of antibiotic-resistant TB is increasing globally; therefore, there is an urgent need to develop host-directed adjunctive therapies to treat TB. Alveolar macrophages, t...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2017-0382OC
更新日期:2018-11-01 00:00:00
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
更新日期:1994-06-01 00:00:00
abstract::Motile cilia are essential for clearance of particulates and pathogens from airways. For effective transport, ciliary motor proteins and axonemal structures interact to generate the rhythmic, propulsive bending, but the mechanisms that produce a dynamic waveform remain incompletely understood. Biomechanical measures o...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2017-0436OC
更新日期:2018-10-01 00:00:00
abstract::Transformation-related protein 63-expressing (p63(+)) basal cells are confined to the trachea in the mouse lung. However, after influenza virus infection or bleomycin treatment, patches of p63(+) cells were observed in the damaged lung parenchyma. To address whether the newly induced p63(+) cells are derived from the ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0327OC
更新日期:2014-03-01 00:00:00
abstract::5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a metabolite of arachidonic acid formed by the oxidation of 5-hydroxy-6,8,11, 14-eicosatetraenoic acid by a highly specific dehydrogenase. 5-oxo-ETE is a chemoattractant for both neutrophils and eosinophils. Although it is not as effective as leukotriene B4 (LTB4) a...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.20.1.3141
更新日期:1999-01-01 00:00:00
abstract::At birth, the mammalian lung is still immature. The alveoli are not yet formed and the interairspace walls contain two capillary layers which are separated by an interstitial core. After alveolarization (first 2 postnatal weeks in rats) the alveolar septa mature: their capillary layers merge, the amount of connective ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.17.3.2737
更新日期:1997-09-01 00:00:00
abstract::The ability of Pseudomonas aeruginosa to form antibiotic-resistant biofilms is thought to account for the inability of current therapies to resolve bacterial infections in the lungs of patients with cystic fibrosis (CF). We recently described a system in which highly antibiotic-resistant P. aeruginosa biofilms grow on...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0299OC
更新日期:2009-09-01 00:00:00
abstract::Hypervascularity is known as an important element of airway remodeling in bronchial asthma. However, it remains obscure how allergic inflammation relates to angiogenesis in the lung. In this study, we examined the in vitro effects of inflammatory cytokines on endothelial cell functions, particularly angiogenesis. Huma...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0162OC
更新日期:2008-02-01 00:00:00
abstract::We examined the mechanisms underlying tachyphylaxis to beta-adrenergic receptor agonists (beta-agonists) in tracheal smooth muscle. Simultaneous measurements of isometric tension and intracellular Ca2+ concentration ([Ca2+]i) using fura-2-loaded guinea pig tracheas showed that the inhibitory effects of isoproterenol (...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0197OC
更新日期:2003-09-01 00:00:00
abstract::Skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease negatively impacts quality of life and survival. Cigarette smoking (CS) is the major risk factor for chronic obstructive pulmonary disease and skeletal muscle dysfunction; however, how CS affects skeletal muscle function remains enigmat...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2019-0106OC
更新日期:2020-02-01 00:00:00
abstract::Nitric oxide (NO) is produced in lung epithelial cells by nitric oxide synthases (NOSs), which can enhance inflammation and edema formation. The inducible NOS (iNOS, type II NOS) has been shown to be increased in lung disorders such as asthma. Therapy for asthma includes antiinflammatory agents such as corticosteroids...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.18.6.3070
更新日期:1998-06-01 00:00:00
abstract::Endothelin-1 is a potent bronchoconstrictor peptide with pro-inflammatory and growth-promoting properties. After exposure of sensitized Brown-Norway rats to six repeated ovalbumin exposures, there was an increase in pro-endothelin (ET)-1 messenger RNA compared with saline-exposed control rats 24 h after the final expo...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.23.5.3909
更新日期:2000-11-01 00:00:00
abstract::Retention kinetics for insoluble particles that deposit in the lung oftentimes resemble a multicomponent process during alveolar clearance, with each component appearing to follow simple first-order kinetics. Inasmuch as alveolar macrophages (AM) are thought to play an important role in particle removal from the lung,...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/1.2.145
更新日期:1989-08-01 00:00:00
abstract::In surgically excised nasal polyps, most epithelial mast cells were formalin sensitive, chloroacetate esterase (CAE) negative, and chymase negative. Thus, this represents a population of mast cells not identified by staining for CAE. On the other hand, most stromal mast cells were formalin resistant and CAE positive, ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/6.1.37
更新日期:1992-01-01 00:00:00
abstract::Sufficient pulmonary surfactant production is required for the fetal-neonatal transition, especially in preterm infants. Neuregulin (NRG) and its transmembrane receptor ErbB4 positively regulate the onset of fetal surfactant synthesis. Details of this signaling process remain to be elucidated. ErbB4 is known to regula...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0179OC
更新日期:2011-10-01 00:00:00