Abstract:
:Over 70% of patients with cystic fibrosis have the DeltaF508 mutation. This protein is a partially functional chloride (Cl-) channel that is prematurely degraded in the endoplasmic reticulum. Specific members of the flavonoid class of compounds have been shown to increase Cl- conductance of wild-type and DeltaF508 cystic fibrosis transmembrane regulator (CFTR). Although flavonoid effects on CFTR processing are unknown, evidence of effects on heat shock proteins, specifically those that have been shown to interact with CFTR, led us to believe that there would be an effect on CFTR processing through modulation of CFTR-chaperone interactions. We sought to determine (i) the effect of apigenin, genistein, kaempferol, and quercetin on CFTR processing in IB3-1 cells (F508/W1282X) and (ii) whether sequential treatment with 4-phenylbutyrate (4-PBA) to increase CFTR processing and flavonoid to directly stimulate CFTR would increase Cl- conductance. Our results show no significant effect on CFTR processing as measured by immunoblotting with 1 microM or 5 microM of apigenin, genistein, kaempferol, or quercetin. However, despite no effect on CFTR processing as determined by immunoblot, immunofluorescence demonstrated a favorable change in the intracellular distribution of CFTR with 24 h treatments of apigenin, kaempferol, and genistein. Furthermore, we observed an increase in Cl- conductance as measured by Cl- efflux in cells that were treated for 24 h with 4-PBA and then assayed with forskolin and 1 microM or 5 microM genistein, and also with cells treated for 24 h with either 4-PBA, 5 microM apigenin, or 1 microM quercetin. Thus, a combination of chronic treatment with 4-PBA or select flavonoids, followed by acute flavonoid exposure, may be beneficial in cystic fibrosis.
journal_name
Am J Respir Cell Mol Biolauthors
Lim M,McKenzie K,Floyd AD,Kwon E,Zeitlin PLdoi
10.1165/rcmb.2002-0086OCkeywords:
subject
Has Abstractpub_date
2004-09-01 00:00:00pages
351-7issue
3eissn
1044-1549issn
1535-4989pii
2002-0086OCjournal_volume
31pub_type
杂志文章abstract::The purpose of this study was to characterize basolateral anion channels in Calu-3 and normal human bronchial epithelial cells, and their role in anion secretion. Patch clamp studies identified an outwardly rectifying Cl- channel (ORCC), which could be activated by the adenosine receptor agonist 5'-(N-ethylcarboxamido...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2003-0109OC
更新日期:2003-12-01 00:00:00
abstract::Tumor necrosis factor-alpha (TNF-alpha) is thought to be important in the development of pulmonary fibrosis. However, surfactant protein-C/TNF-alpha transgenic mice do not spontaneously develop pulmonary fibrosis but instead develop alveolar enlargement and loss of elastic recoil. We hypothesized that overexpression o...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0046OC
更新日期:2003-12-01 00:00:00
abstract::Silicosis is a chronic lung disease induced by the inhalation of crystalline silica. Exposure of cultured macrophages to crystalline silica leads to cell death; however, the mechanism of cell-particle interaction, the fate of particles, and the cause of death are unknown. Time-lapse imaging shows that mouse macrophage...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2008-0046OC
更新日期:2008-11-01 00:00:00
abstract::Lung morphometry was introduced over 50 years ago to provide quantitative evaluation of the lung structure. The existing parameters, such as mean linear intercept and destructive index, suffer from simplistic data interpretation and a subjective data acquisition process. To overcome these existing shortcomings, parenc...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2016-0143OC
更新日期:2016-11-01 00:00:00
abstract::Macrophage inflammatory proteins 1 alpha and 2 (MIP-1 alpha, MIP-2) are members of a growing family of cytokines thought to play a role in host defense. MIP-1 alpha and MIP-2 were previously identified in the mouse and shown to stimulate inflammatory cell recruitment. To better understand the potential role of MIP-1 a...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/8.3.311
更新日期:1993-03-01 00:00:00
abstract::In addition to inhibiting proliferation and causing enlargement of bovine pulmonary artery endothelial cells in culture, porcine platelet transforming growth factor-beta 1 (TGF-beta 1) (2 ng/ml) lowered glutathione (GSH) of these cells by 48% after 96 h in culture when GSH levels were normalized for cell counts. This ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/6.4.364
更新日期:1992-04-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) has been associated with heterozygosity for the Z and S alleles of the alpha1-antitrypsin gene in some studies, but these observations have not been confirmed by others. Cigarette smoking is the major risk factor for COPD and may have been a confounding factor in many of th...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.20.2.3177
更新日期:1999-02-01 00:00:00
abstract::Previous studies have demonstrated that high tidal volumes can cause interstitial and alveolar edema, with degradation of pulmonary epithelial barrier integrity. Separate studies have shown that F-actin disruption and decreased intracellular ATP (ATP(i)) levels in the nonpulmonary epithelium can increase tight junctio...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.25.5.4486
更新日期:2001-11-01 00:00:00
abstract::Chlamydia infections are frequent causes of respiratory illness, particularly pneumonia in infants, and are linked to permanent reductions in lung function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incom...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2015-0204OC
更新日期:2016-04-01 00:00:00
abstract::The cytokine mRNA profiles of primary (arising from inhaled bacilli) and secondary (arising from hematogenous reseeding of the lung) granulomas from the lung lobes of bacillus Calmette-Guérin (BCG)-vaccinated and unimmunized guinea pigs challenged with virulent Mycobacterium tuberculosis by the pulmonary route were as...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0326OC
更新日期:2008-04-01 00:00:00
abstract::T helper 2 (Th2)-like cytokines are thought to play a crucial role in the pathogenesis of airway inflammation in atopic asthma, leading to bronchial hyperresponsiveness. To investigate the role of the principal Th2 cytokine interleukin-4 (IL-4) in asthma, we examined the allergen-induced changes in airway morphology a...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.12.3.7873190
更新日期:1995-03-01 00:00:00
abstract::Modification of tyrosine residues and formation of 3-nitrotyrosine is one of the most commonly identified effects of reactive nitrogen species on proteins. In this study we evaluated the presence and localization of tyrosine nitration in various ventilatory and limb muscles. We also assessed the contribution of the ne...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.26.4.4634
更新日期:2002-04-01 00:00:00
abstract::Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among single-nucleotide polymorphisms (SNPs) in genes of the histamine ...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2014-0493OC
更新日期:2015-12-01 00:00:00
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::In this study, we investigated the effect of the novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) on the growth of human lung carcinoma cell lines. AHPN inhibits the proliferation of all cell lines tested, irrespective of the lung tumor type, in a concentration- and time-de...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.18.3.2974
更新日期:1998-03-01 00:00:00
abstract::The insulin-like growth factor (IGF)-II/mannose-6-phosphate (M6P) receptor, which targets acid hydrolases to lysosomes, is a multifunctional protein with separate binding sites for IGF-II and M6P. The purpose of this study was to determine if alveolar macrophages (AM) and their precursor cells, blood monocytes, expres...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/4.6.555
更新日期:1991-06-01 00:00:00
abstract::SLC6A14-mediated l-arginine transport has been shown to augment the residual anion channel activity of the major mutant, F508del-CFTR, in the murine gastrointestinal tract. It is not yet known if this transporter augments residual and pharmacological corrected F508del-CFTR in primary airway epithelia. We sought to det...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2019-0094OC
更新日期:2019-12-01 00:00:00
abstract::Enzymes which exhibit core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT) activity play important roles in physiologic processes including the inflammatory response and immune system function, and C2GnT activity is regulated during processes, such as T cell activation and cellular differentiation. In this study, we...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2002-0147OC
更新日期:2003-07-01 00:00:00
abstract::Airway surface fluids are mainly secreted from submucosal glands, and play important roles in the defense of airways via the up-regulation of mucociliary transport, resulting in an exclusion of many microbes or foreign substances. Although there are many articles concerning the importance of Toll-like receptors (TLRs)...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2011-0020OC
更新日期:2011-11-01 00:00:00
abstract::The biologic activity of substance P has been demonstrated to be limited both in in vivo and in vitro by a membrane-bound protease, neutral endopeptidase (EC 3.4.24.11). The interaction of substance P with its receptor on guinea pig lung tissues was studied in the presence of an inhibitor of neutral endopeptidase unde...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/1.4.269
更新日期:1989-10-01 00:00:00
abstract::Endotoxins represent one of the most potent classes of microbial immunoactive components that can cause pulmonary inflammation. The aim of this study was to compare the inflammatory potency of two types of Neisseria meningitidis endotoxins (lipooligosaccharides) in lungs: wild type (hexaacylated, LOS(wt)) and mutant t...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2007-0418OC
更新日期:2008-06-01 00:00:00
abstract::Hexavalent chromium (Cr[VI]) is classified by the International Agency for Research on Cancer as a group I carcinogen. Although the U.S. Occupational Safety and Health Administration was obliged to reduce the permissible exposure limit (PEL), it was reported that U.S. workers continue to be exposed to dangerously high...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2005-0213OC
更新日期:2005-12-01 00:00:00
abstract::Nitrogen dioxide (NO2) is a pollutant of both outdoor and indoor atmospheres that has the potential to alter alveolar epithelial permeability. In order to assess alterations in the protein content of alveolar lining fluid induced by brief (3-h) exposures to low-level NO2, normal volunteers were exposed sequentially to...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/1.6.499
更新日期:1989-12-01 00:00:00
abstract::Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and are a major source of vascular endothelial growth factor (VEGF), which modulates the maintenance of pulmonary microvasculature. Prostaglandin E(2) (PGE(2)) acts on a set of E-prostanoid (EP) receptors that activate multiple sig...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0115OC
更新日期:2012-02-01 00:00:00
abstract::To identify mechanisms that allow p185HER2 expression in lung cancer, we performed Western, Southern, and Northern blot analyses of 14 cell lines derived from human non-small cell lung carcinomas and one cell line derived from a human mesothelioma. Human bronchiole epithelial cells and rat type II pneumocytes were fou...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb/6.4.359
更新日期:1992-04-01 00:00:00
abstract::Recently, investigators demonstrated associations between fine particulate matter (PM)-associated metals and adverse health effects. Residual oil fly ash (ROFA), a waste product of fossil fuel combustion from boilers, is rich in the transition metals Fe, Ni, and V, and when released as a fugitive particle, is an impor...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2009-0456OC
更新日期:2011-02-01 00:00:00
abstract::Increased activity of lung epithelial sodium channels (ENaCs) contributes to the pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial lining fluid reabsorption. Inter-α-inhibitor (IαI), a serum protease inhibitor, may decrease ENaC activity by preventing its cleavage by serine proteases. High c...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2013-0215OC
更新日期:2014-05-01 00:00:00
abstract::Alveolar macrophages (AMs) play an important role in the regulation of the local immune reactivity in the lung. It was previously shown that exposure of rats to mild inescapable electrical footshock stress (20 min, 4 shocks/min, 5 s/shock, 0.8 mAmp) leads to apparent changes in the activity of AMs upon stimulation, re...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/ajrcmb.19.5.3103
更新日期:1998-11-01 00:00:00
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
更新日期:2002-03-01 00:00:00
abstract::A subset of workers in swine confinement facilities develops chronic respiratory disease. An aqueous extract of dust from these facilities (hogbarn dust extract [HDE]) induces IL-6 and IL-8 release and several other responses in isolated airway epithelial cells. The cell membrane receptors by which HDE initiates these...
journal_title:American journal of respiratory cell and molecular biology
pub_type: 杂志文章
doi:10.1165/rcmb.2010-0419OC
更新日期:2011-10-01 00:00:00