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 hyperplasia and mucin hypersecretion in normal human bronchial epithelial (NHBE) cells. NHBE cells were cultured to differentiation at an air-liquid interface with IL-13 plus clarithromycin or vehicle. Histochemical analysis was performed using H&E staining, periodic acid-Schiff (PAS) staining, and MUC5AC immunostaining. MUC5AC synthesis was assayed using RT-PCR and ELISA. Western blotting was used to evaluate signaling pathways. IL-13 significantly increased the number of PAS-positive, MUC5AC-positive goblet cells, and this was significantly attenuated by clarithromycin at concentrations greater than 8 μg/ml (P < 0.01). Clarithromycin also dose-dependently decreased MUC5AC mRNA expression induced by IL-13 (P < 0.001), and, at 24 μg/ml, clarithromycin significantly attenuated the amount of MUC5AC protein in cell supernatants (P < 0.01). Western blotting showed that clarithromycin affected IL-13 receptor janus kinase signal transducers, activators of transcription6 (STAT6), and epidermal growth factor receptor mitogen-activated protein kinase signaling and that inhibition of these pathways by clarithromycin decreased goblet cell hyperplasia via nuclear factor-κB inactivation. We conclude that clarithromycin inhibits goblet cell hyperplasia and may directly regulate mucus secretion by IL-13 in NHBE cells.

authors

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

doi

10.1165/rcmb.2010-0327OC

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

1075-83

issue

5

eissn

1044-1549

issn

1535-4989

pii

2010-0327OC

journal_volume

45

pub_type

杂志文章
  • Involvement of IL-5 in a murine model of allergic pulmonary inflammation: prophylactic and therapeutic effect of an anti-IL-5 antibody.

    abstract::Interleukin-5 (IL-5) is important in the control of differentiation, migration, and activation of eosinophils. In order to study the role of IL-5 in the development of eosinophilic inflammation of the airways, we have used a monoclonal antibody to murine IL-5 (TRFK-5) in a murine model of allergic pulmonary inflammati...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.13.3.7654390

    authors: Kung TT,Stelts DM,Zurcher JA,Adams GK 3rd,Egan RW,Kreutner W,Watnick AS,Jones H,Chapman RW

    更新日期:1995-09-01 00:00:00

  • Tetrodotoxin does not block the epithelium-dependent release of prostaglandin E2 induced by electrical field stimulation in isolated ferret trachea.

    abstract::Electrical field stimulation (EFS) has previously been shown to induce the release of prostaglandin (PG) E2 from ferret tracheal epithelium. We have now conducted a study to see whether this effect of EFS is due to the activation of nerves or whether it is a non-neural effect. The release of PGE2 and 6-keto-PGF1 alpha...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/4.3.243

    authors: Ullman A,Ciabattoni G,Svedmyr N,Skoogh BE,Löfdahl CG

    更新日期:1991-03-01 00:00:00

  • Effects of mitochondrial potassium channel and membrane potential on hypoxic human pulmonary artery smooth muscle cells.

    abstract::Chronic hypoxia induces proliferation of human pulmonary artery smooth muscle cells (hPASMCs), leading to remodeling and pulmonary hypertension, but the mechanism remains unclear. The present study tested the roles of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) and mitochondrial membrane potential (Delt...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0017OC

    authors: Hu HL,Zhang ZX,Chen CS,Cai C,Zhao JP,Wang X

    更新日期:2010-06-01 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

  • Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking.

    abstract::Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue gr...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2014-0083OC

    authors: Tsuji T,Kelly NJ,Takahashi S,Leme AS,Houghton AM,Shapiro SD

    更新日期:2014-12-01 00:00:00

  • Age-related decrease in respiratory muscle mitochondrial function in rats.

    abstract::The purpose of this study was to elucidate the effects of aging on diaphragmatic mitochondrial function. Diaphragm mitochondria were prepared from specific pathogen-free rats aged 7 wk (n = 7), 35 wk (n = 7), and 55 wk (n = 7). The activities of various portions of the mitochondrial electron transport chain, i.e., com...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/6.1.88

    authors: Torii K,Sugiyama S,Takagi K,Satake T,Ozawa T

    更新日期:1992-01-01 00:00:00

  • Oxysterols trigger ABCA1-mediated basolateral surfactant efflux.

    abstract::Surfactant is an apically-secreted surface-active material containing primarily disaturated phosphatidylcholine (DSPtdCho) that is released from alveolar epithelia into the alveolus. Surfactant deficiency is an important aspect of inflammatory lung disease and may result from extravasation of serum lipoproteins into t...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2004-0038OC

    authors: Agassandian M,Mathur SN,Zhou J,Field FJ,Mallampalli RK

    更新日期:2004-08-01 00:00:00

  • Upregulation of interleukin-4 receptor by interferon-gamma: enhanced interleukin-4-induced eotaxin-3 production in airway epithelium.

    abstract::Airway epithelial cells produce a number of chemokines, including eotaxins. Among the three known eotaxins, T helper (Th) type 2 cytokines have been observed to induce the expression of eotaxin-3 mRNA. This study investigated the effect of interferon (IFN)-gamma, a Th1 cytokine, on Th2 cytokine-induced eotaxin-3 produ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2004-0128OC

    authors: Yamamoto S,Kobayashi I,Tsuji K,Nishi N,Muro E,Miyazaki M,Zaitsu M,Inada S,Ichimaru T,Hamasaki Y

    更新日期:2004-10-01 00:00:00

  • Reduction of glutathione is associated with growth restriction and enlargement of bovine pulmonary artery endothelial cells produced by transforming growth factor-beta 1.

    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

    authors: White AC,Das SK,Fanburg BL

    更新日期:1992-04-01 00:00:00

  • Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery.

    abstract::Primary pulmonary hypertension is characterized by increased pulmonary vascular resistance and smooth muscle proliferation. Stable analogs are increasingly being used to treat this disease, although no data exists comparing their effects on proliferation. We therefore investigated the antiproliferative activity of sev...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.26.2.4695

    authors: Clapp LH,Finney P,Turcato S,Tran S,Rubin LJ,Tinker A

    更新日期:2002-02-01 00:00:00

  • Mucin biosynthesis: epidermal growth factor downregulates core 2 enzymes in a human airway adenocarcinoma cell line.

    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

    authors: Beum PV,Bastola DR,Cheng PW

    更新日期:2003-07-01 00:00:00

  • Neutrophil-endothelial interactions mediate angiopoietin-2-associated pulmonary endothelial cell dysfunction in indirect acute lung injury in mice.

    abstract::Unresolved inflammation in the lung is thought to elicit loss of endothelial cell (EC) barrier integrity and impaired lung function. We have shown, in a mouse model of shock/sepsis, that neutrophil interactions with resident pulmonary cells appear central to the pathogenesis of indirect acute lung injury (iALI). Norma...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0148OC

    authors: Lomas-Neira J,Venet F,Chung CS,Thakkar R,Heffernan D,Ayala A

    更新日期:2014-01-01 00:00:00

  • Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice.

    abstract::Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characteri...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.23.4.4199

    authors: Ewart SL,Kuperman D,Schadt E,Tankersley C,Grupe A,Shubitowski DM,Peltz G,Wills-Karp M

    更新日期:2000-10-01 00:00:00

  • Attachment of influenza A virus to ferret tracheal epithelium at different maturational stages.

    abstract::Influenza virus attaches primarily to ciliated cells in mature airways epithelium. This process is mediated by a viral envelope glycoprotein (hemagglutinin) that binds to sialic acid-containing receptors in the apical membrane of host cells. The purpose of this study was to determine the cellular distribution of these...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/4.1.82

    authors: Piazza FM,Carson JL,Hu SC,Leigh MW

    更新日期:1991-01-01 00:00:00

  • Platelet-activating factor induces airway mucin release via activation of protein kinase C: evidence for translocation of protein kinase C to membranes.

    abstract::Platelet-activating factor (PAF), a proinflammatory lipid mediator, is a potent airway mucin secretagogue. This study assessed the role of protein kinase C (PKC) in PAF-induced mucin release from primary cultures of feline tracheal epithelial cells (FTEC). Mucin secretion was quantitated by enzyme-linked immunosorbent...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.11.2.8049080

    authors: Larivée P,Levine SJ,Martinez A,Wu T,Logun C,Shelhamer JH

    更新日期:1994-08-01 00:00:00

  • Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis.

    abstract::Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/9.4.455

    authors: Bédard M,McClure CD,Schiller NL,Francoeur C,Cantin A,Denis M

    更新日期:1993-10-01 00:00:00

  • Hyperoxia alone causes changes in lung proteoglycans and hyaluronan in neonatal rat pups.

    abstract::Specific changes in composition and content of lung extracellular matrix (ECM) proteoglycans (PGs) and hyaluronan (HA) have been observed during the acute response to damage in several forms of injury including infant respiratory distress syndrome (IRDS). These ECM components are thought to modulate the healing respon...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.13.6.7576700

    authors: Juul SE,Krueger RC Jr,Scofield L,Hershenson MB,Schwartz NB

    更新日期:1995-12-01 00:00:00

  • Pneumocystis carinii expresses an active Rtt109 histone acetyltransferase.

    abstract::Species in the genus Pneumocystis can cause severe pneumonia in immune-compromised hosts. The identification of specific targets present in Pneumocystis species, but lacking in mammalian hosts, is paramount to developing new means to treat this infection. One such potential protein is Rtt109, which is a type of histon...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2009-0443OC

    authors: Kottom TJ,Han J,Zhang Z,Limper AH

    更新日期:2011-06-01 00:00:00

  • Tumor necrosis factor-alpha stimulates human Clara cell secretory protein production by human airway epithelial cells.

    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

    authors: Yao XL,Levine SJ,Cowan MJ,Logun C,Shelhamer JH

    更新日期:1998-10-01 00:00:00

  • Nonmuscle myosin light chain kinase regulates murine asthmatic inflammation.

    abstract::Myosin light chain kinase (MLCK; gene code, MYLK) is a multifunctional enzyme involved in isoform-specific nonmuscle (nm) and smooth muscle contraction, inflammation, and vascular permeability, processes directly relevant to asthma pathobiology. In this report, we highlight the contribution of the nm isoform (nmMLCK) ...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2013-0434OC

    authors: Wang T,Moreno-Vinasco L,Ma SF,Zhou T,Shimizu Y,Sammani S,Epshtein Y,Watterson DM,Dudek SM,Garcia JG

    更新日期:2014-06-01 00:00:00

  • Regulated production of the T helper 2-type T-cell chemoattractant TARC by human bronchial epithelial cells in vitro and in human lung xenografts.

    abstract::The chemokine TARC is a ligand for the chemokine receptor CCR4 expressed on T helper (Th)2-type CD4 T cells. Allergic airway inflammation is characterized by a local increase in cells secreting Th2-type cytokines. We hypothesized that bronchial epithelial cells may be a source of chemokines known to chemoattract Th2 c...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.24.4.4360

    authors: Berin MC,Eckmann L,Broide DH,Kagnoff MF

    更新日期:2001-04-01 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

  • MicroRNAs in pulmonary arterial hypertension.

    abstract::Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章,评审

    doi:10.1165/rcmb.2014-0166TR

    authors: Zhou G,Chen T,Raj JU

    更新日期:2015-02-01 00:00:00

  • Interleukin-9 upregulates mucus expression in the airways.

    abstract::Interleukin (IL)-9 has recently been shown to play an important role in allergic disease because its expression is strongly associated with the degree of airway responsiveness and the asthmatic-like phenotype. IL-9 is a pleiotropic cytokine that is active on many cell types involved in the allergic immune response. Mu...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.22.6.3927

    authors: Louahed J,Toda M,Jen J,Hamid Q,Renauld JC,Levitt RC,Nicolaides NC

    更新日期:2000-06-01 00:00:00

  • Tissue inhibitor of metalloproteinases-3 moderates the proinflammatory status of macrophages.

    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

    authors: Gill SE,Gharib SA,Bench EM,Sussman SW,Wang RT,Rims C,Birkland TP,Wang Y,Manicone AM,McGuire JK,Parks WC

    更新日期:2013-11-01 00:00:00

  • Sodium fluoride induces phosphoinositide hydrolysis, Ca2+ mobilization, and prostacyclin synthesis in cultured human endothelium: further evidence for regulation by a pertussis toxin-insensitive guanine nucleotide-binding protein.

    abstract::The role of guanine nucleotide-binding proteins in the induction of prostacyclin synthesis by stimulated endothelial cells is incompletely understood. We report that sodium fluoride (NaF), a potent activator of cellular guanine nucleotide-binding proteins, affected time- and concentration-dependent generation of prost...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb/5.2.113

    authors: Garcia JG,Dominguez J,English D

    更新日期:1991-08-01 00:00:00

  • MD-2-dependent pulmonary immune responses to inhaled lipooligosaccharides: effect of acylation state.

    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

    authors: Hadina S,Weiss JP,McCray PB Jr,Kulhankova K,Thorne PS

    更新日期:2008-06-01 00:00:00

  • Adhesion of bovine airway smooth muscle cells activates extracellular signal-regulated kinases.

    abstract::Extracellular signal-regulated kinases (ERKs) phosphorylate and regulate cytoskeletal components of contractile cells and have been implicated in integrin-mediated adhesion. In this study, we examined the contributions of adherence, cell flattening, and cytoskeletal reorganization to adhesion-induced ERK activation in...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.17.4.2702

    authors: Heuertz RM,Hamann KJ,Hershenson MB,Leff AR

    更新日期:1997-10-01 00:00:00

  • p42/44 Mitogen-activated protein kinase regulated by p53 and nitric oxide in human pulmonary arterial smooth muscle cells.

    abstract::Although nitric oxide (NO) is known to inhibit vascular smooth muscle cell proliferation, the subcellular molecular mechanisms involved with the inhibitory signal transduction pathways are uncertain. We investigated the effect of exogenous NO on cell proliferation and the expression of p53, p21, and phosphorylated p42...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/rcmb.2003-0397OC

    authors: Mizuno S,Kadowaki M,Demura Y,Ameshima S,Miyamori I,Ishizaki T

    更新日期:2004-08-01 00:00:00

  • Migration of neutrophils across human pulmonary endothelial cells is not blocked by matrix metalloproteinase or serine protease inhibitors.

    abstract::It has long been speculated that neutrophils deploy proteases to digest subendothelial matrix as they migrate from the bloodstream. Direct evidence for the involvement of proteases in neutrophil transendothelial migration is, however, lacking. To address this issue we used transmission electron microscopy to verify th...

    journal_title:American journal of respiratory cell and molecular biology

    pub_type: 杂志文章

    doi:10.1165/ajrcmb.20.6.3539

    authors: Mackarel AJ,Cottell DC,Russell KJ,FitzGerald MX,O'Connor CM

    更新日期:1999-06-01 00:00:00