Chitinase 3-like-1 regulates both visceral fat accumulation and asthma-like Th2 inflammation.

Abstract:

RATIONALE:Obesity, especially truncal obesity, is a risk factor for asthma incidence, prevalence, and severity. Chitinase 3-like-1 (Chi3l1) is an evolutionarily conserved moiety that plays a critical role in antipathogen and Th2 responses. However, the mechanisms that underlie the association between asthma and obesity and the role(s) of Chi3l1 in fat accumulation have not been defined. OBJECTIVES:To determine whether Chi3l1 is regulated by a high-fat diet (HFD) and simultaneously plays an important role(s) in the pathogenesis of asthma and obesity. METHODS:We evaluated the regulation of Chi3l1 by an HFD and Th2 inflammation. We also used genetically modified mice to define the roles of Chi3l1 in white adipose tissue (WAT) accumulation and Th2 inflammation and blockers of sirtuin 1 (Sirt1) to define its roles in these responses. Finally, the human relevance of these findings was assessed with a case-control study involving obese and lean control subjects and those with asthma. MEASUREMENTS AND MAIN RESULTS:These studies demonstrate that an HFD and aeroallergen challenge augment the expression of WAT and pulmonary Chi3l1. Chi3l1 also played a critical role in WAT accumulation and lung Th2 inflammation. In addition, Chi3l1 inhibited Sirt1 expression, and the deficient visceral fat and Th2 responses in Chi3l1 null mice were reversed by Sirt1 inhibition. Finally, serum and sputum Chi3l1 were positively associated with truncal adiposity, and serum Chi3l1 was associated with persistent asthma and low lung function in obese subjects with asthma. CONCLUSIONS:Chi3l1 is induced by an HFD and Th2 inflammation, and simultaneously contributes to the genesis of obesity and asthma.

authors

Ahangari F,Sood A,Ma B,Takyar S,Schuyler M,Qualls C,Dela Cruz CS,Chupp GL,Lee CG,Elias JA

doi

10.1164/rccm.201405-0796OC

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

746-57

issue

7

eissn

1073-449X

issn

1535-4970

journal_volume

191

pub_type

杂志文章
  • Nasal polyp-derived superoxide anion: dose-dependent inhibition by nitric oxide and pathophysiological implications.

    abstract::The epithelium of the paranasal sinuses produces nitric oxide (NO), which probably plays a major role in the nonspecific defense of these cavities through its bacteriostatic and cilia motility stimulation properties. Abundant eosinophils of nasal polyps potentially generate superoxide anion (O2-*), but NO and O2-* ina...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.163.1.2002125

    authors: Pasto M,Serrano E,Urocoste E,Barbacanne MA,Guissani A,Didier A,Delisle MB,Rami J,Arnal JF

    更新日期:2001-01-01 00:00:00

  • Exposure-response relationship between passive smoking and adult pulmonary function.

    abstract::The effects of exposure to environmental tobacco smoke (ETS) on pulmonary function were investigated in a random sample of 1,033 adults aged 40 to 69 yr from a residential area in Beijing. Compared with those not exposed, those exposed to ETS either at home or at work were associated with a 102-ml (SE = 40 ml) reducti...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.151.1.7812570

    authors: Xu X,Li B

    更新日期:1995-01-01 00:00:00

  • Physiological risk factors for severe high-altitude illness: a prospective cohort study.

    abstract:RATIONALE:An increasing number of persons, exposed to high altitude for leisure, sport, or work, may suffer from severe high-altitude illness. OBJECTIVES:To assess, in a large cohort of subjects, the association between physiological parameters and the risk of altitude illness and their discrimination ability in a ris...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201108-1396OC

    authors: Richalet JP,Larmignat P,Poitrine E,Letournel M,Canouï-Poitrine F

    更新日期:2012-01-15 00:00:00

  • Autologous transfusion of stored red blood cells increases pulmonary artery pressure.

    abstract:RATIONALE:Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction. OBJECTIVES:We hypothesized that transfu...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.1164/rccm.201405-0850OC

    authors: Berra L,Pinciroli R,Stowell CP,Wang L,Yu B,Fernandez BO,Feelisch M,Mietto C,Hod EA,Chipman D,Scherrer-Crosbie M,Bloch KD,Zapol WM

    更新日期:2014-10-01 00:00:00

  • Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis.

    abstract:RATIONALE:The IL-1 receptor-associated kinase (IRAK-1) plays a central role in TLR2- and TLR4-induced activation of nuclear factor (NF)-kappaB, a critical event in the transcriptional regulation of many sepsis-associated proinflammatory mediators. There are two haplotypes for the IRAK-1 gene in Caucasians, with the var...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200603-341OC

    authors: Arcaroli J,Silva E,Maloney JP,He Q,Svetkauskaite D,Murphy JR,Abraham E

    更新日期:2006-06-15 00:00:00

  • Panic anxiety, dyspnea, and respiratory disease. Theoretical and clinical considerations.

    abstract::There is intriguing evidence suggesting pathophysiologic relationships among dyspnea, hyperventilation, and panic anxiety. The symptoms of panic attacks and pulmonary disease overlap, so that panic anxiety can reflect underlying cardiopulmonary disease and dyspnea can reflect an underlying anxiety disorder. The pathog...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1164/ajrccm.154.1.8680700

    authors: Smoller JW,Pollack MH,Otto MW,Rosenbaum JF,Kradin RL

    更新日期:1996-07-01 00:00:00

  • Keratinocyte growth factor promotes epithelial survival and resolution in a human model of lung injury.

    abstract:RATIONALE:Increasing epithelial repair and regeneration may hasten resolution of lung injury in patients with the acute respiratory distress syndrome (ARDS). In animal models of ARDS, keratinocyte growth factor (KGF) reduces injury and increases epithelial proliferation and repair. The effect of KGF in the human alveol...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.1164/rccm.201310-1892OC

    authors: Shyamsundar M,McAuley DF,Ingram RJ,Gibson DS,O'Kane D,McKeown ST,Edwards A,Taggart C,Elborn JS,Calfee CS,Matthay MA,O'Kane CM

    更新日期:2014-06-15 00:00:00

  • Urine bombesin-like peptide elevation precedes clinical evidence of bronchopulmonary dysplasia.

    abstract::Bronchopulmonary dysplasia (BPD) is a chronic lung disease of very low birth weight infants, associated with oxygen therapy, barotrauma, and/or infections. Improved medical care has led to a paradoxically increased incidence of BPD due to greater infant survival. Early prediction of BPD has proven challenging. Increas...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.165.8.2108044

    authors: Cullen A,Van Marter LJ,Allred EN,Moore M,Parad RB,Sunday ME

    更新日期:2002-04-15 00:00:00

  • Association of asthma with serum IgE and skin test reactivity to allergens among children living at high altitude. Tickling the dragon's breath.

    abstract::Asthma in children and young adults is strongly associated with immediate hypersensitivity to indoor allergens, notably those derived from the house dust mite. In addition, outdoor air pollution is considered to aggravate existing asthma. We investigated the prevalence of asthma and the pattern of allergen sensitizati...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.151.5.7735590

    authors: Sporik R,Ingram JM,Price W,Sussman JH,Honsinger RW,Platts-Mills TA

    更新日期:1995-05-01 00:00:00

  • Optimization of aerosol deposition by pressure support in children with cystic fibrosis: an experimental and clinical study.

    abstract::Nebulized aerosols are commonly used to deliver drugs into the lungs of patients with cystic fibrosis (CF). The aim of this study was to assess the effectiveness of pressure-support (PS) ventilation in increasing aerosol deposition within the lungs of children with CF. An in vitro study demonstrated the feasibility of...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章

    doi:10.1164/ajrccm.162.6.2003069

    authors: Fauroux B,Itti E,Pigeot J,Isabey D,Meignan M,Ferry G,Lofaso F,Willemot JM,Clément A,Harf A

    更新日期:2000-12-01 00:00:00

  • Aspects on the interaction of Streptococcus pneumoniae and Haemophilus influenzae with human respiratory tract mucosa.

    abstract::Haemophilus influenzae and Streptococcus pneumoniae are common causes of respiratory tract infections. H. influenzae attach to receptor epitopes in mucins and in epithelial cell membranes. Attachment is followed by an epithelial cell cytokine response. Secreted cytokines then initiate inflammation, upset the integrity...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm/154.4_Pt_2.S187

    authors: Håkansson A,Carlstedt I,Davies J,Mossberg AK,Sabharwal H,Svanborg C

    更新日期:1996-10-01 00:00:00

  • All-cause mortality rate in patients with idiopathic pulmonary fibrosis. Implications for the design and execution of clinical trials.

    abstract:RATIONALE:FVC has emerged as a standard primary endpoint in clinical trials evaluating novel therapies for patients with idiopathic pulmonary fibrosis (IPF). However, it has recently been proposed that all-cause mortality or a composite comprised of all-cause mortality and all-cause nonelective hospitalization be adopt...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201311-1951OC

    authors: King TE Jr,Albera C,Bradford WZ,Costabel U,du Bois RM,Leff JA,Nathan SD,Sahn SA,Valeyre D,Noble PW

    更新日期:2014-04-01 00:00:00

  • A case of pulmonary AV fistula. Possible involvement of adenosine in hyperventilation.

    abstract::A 21-yr-old man with multiple pulmonary AV fistulae presented with moderate hypoxemia with chronic hyperventilation, which continued even after sufficient oxygenation by 100% O2 inhalation. The infusion of aminophylline, an adenosine receptor blocker, not only increased PaCO2 from 35 to 39 mm Hg but also depressed the...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1164/ajrccm.150.6.7952640

    authors: Kobayashi S,Nishimura M,Nasuhara Y,Miyamoto K,Kawakami Y

    更新日期:1994-12-01 00:00:00

  • Endotoxin contamination causes neutrophilia following pulmonary allergen challenge.

    abstract::Segmental bronchoprovocation (SBP) with allergen was used in an attempt to study eosinophils recruited to the airway 24 h after challenge. Unexpectedly, in the first four patients, neutrophils (rather than eosinophils) were recruited in the bronchoalveolar lavage (BAL) fluids, and we hypothesized that the allergen ext...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.149.6.8004300

    authors: Hunt LW,Gleich GJ,Ohnishi T,Weiler DA,Mansfield ES,Kita H,Sur S

    更新日期:1994-06-01 00:00:00

  • A decision rule for diagnostic testing in obstructive sleep apnea.

    abstract::Obstructive sleep apnea (OSA) is traditionally diagnosed using overnight polysomnography. Decision rules may provide an alternative to polysomnography. A consecutive series of patients referred to a tertiary sleep center underwent prospective evaluation with the upper airway physical examination protocol, followed by ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200112-110OC

    authors: Tsai WH,Remmers JE,Brant R,Flemons WW,Davies J,Macarthur C

    更新日期:2003-05-15 00:00:00

  • Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population.

    abstract::Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components, and several candidate genes have been reported to be linked to atopy in Caucasian populations. We conducted a study of linkage between asthma and markers on chromosomes 5q31-q33 and 11q13 in 68 Japa...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.156.5.9702084

    authors: Noguchi E,Shibasaki M,Arinami T,Takeda K,Maki T,Miyamoto T,Kawashima T,Kobayashi K,Hamaguchi H

    更新日期:1997-11-01 00:00:00

  • Nitric oxide modulates interleukin-1beta and tumor necrosis factor-alpha synthesis by alveolar macrophages in pulmonary tuberculosis.

    abstract::Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha released from alveolar macrophages (AM) in pulmonary tuberculosis (TB) are important in host defense against mycobacterial infection. Nitric oxide (NO) production is enhanced in AM of TB patients. We examined whether NO was implicated in (IL)-1beta and TNF-a...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.161.1.9902113

    authors: Kuo HP,Wang CH,Huang KS,Lin HC,Yu CT,Liu CY,Lu LC

    更新日期:2000-01-01 00:00:00

  • Inhaled PGE2 prevents aspirin-induced bronchoconstriction and urinary LTE4 excretion in aspirin-sensitive asthma.

    abstract::Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinar...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1164/ajrccm.153.2.8564100

    authors: Sestini P,Armetti L,Gambaro G,Pieroni MG,Refini RM,Sala A,Vaghi A,Folco GC,Bianco S,Robuschi M

    更新日期:1996-02-01 00:00:00

  • Recruitment and derecruitment during acute respiratory failure: an experimental study.

    abstract::We aimed to elucidate the relationships between pleural (Ppl), esophageal (Pes), and superimposed gravitational pressures in acute lung injury, and to understand the mechanisms of recruitment and derecruitment. In six dogs with oleic acid respiratory failure, we measured Pes and Ppl in the uppermost, middle, and most ...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.164.1.2007010

    authors: Pelosi P,Goldner M,McKibben A,Adams A,Eccher G,Caironi P,Losappio S,Gattinoni L,Marini JJ

    更新日期:2001-07-01 00:00:00

  • A randomized controlled trial of intravenous montelukast in acute asthma.

    abstract::Many patients with acute asthma do not respond adequately to currently accepted therapy, including oxygen, beta-agonists, and corticosteroids. Leukotriene receptor antagonists such as montelukast have demonstrated efficacy in chronic asthma, but their efficacy in acute asthma is unknown. In this randomized, double-bli...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1164/rccm.200208-802OC

    authors: Camargo CA Jr,Smithline HA,Malice MP,Green SA,Reiss TF

    更新日期:2003-02-15 00:00:00

  • Mite and cat allergen levels in homes and severity of asthma.

    abstract::The relationships between mite and cat allergen levels in the home, skin test reactivity, and severity of asthma were explored in 120 asthmatic subjects, 57 in Vancouver and 63 in Winnipeg. Patients in the two cities were similar in age, gender distribution, and severity of asthma. Skin tests were performed using 13 c...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.152.6.8520740

    authors: Chan-Yeung M,Manfreda J,Dimich-Ward H,Lam J,Ferguson A,Warren P,Simons E,Broder I,Chapman M,Platts-Mills T

    更新日期:1995-12-01 00:00:00

  • Semirecumbent position protects from pulmonary aspiration but not completely from gastroesophageal reflux in mechanically ventilated patients.

    abstract::The aim of this study was to evaluate the effect of two body positions (supine and semirecumbency) on the dynamics of gastroesophageal reflux (GER) in 15 patients requiring mechanical ventilation and having a nasogastric tube in place. Samples of gastric contents, pharyngeal and bronchial secretions, and blood were ob...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1164/ajrccm.152.4.7551400

    authors: Orozco-Levi M,Torres A,Ferrer M,Piera C,el-Ebiary M,de la Bellacasa JP,Rodriguez-Roisin R

    更新日期:1995-10-01 00:00:00

  • Airway inflammation and remodeling in asthma. Lessons from interleukin 11 and interleukin 13 transgenic mice.

    abstract::Noninflammatory structural alterations, variously referred to as airway remodeling, are well documented in the asthmatic airway. However, the pathogenesis of these alterations, the importance of airway remodeling in generating the asthma phenotype, and the natural history of airway remodeling responses have not been a...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.164.supplement_2.2106070

    authors: Zhu Z,Lee CG,Zheng T,Chupp G,Wang J,Homer RJ,Noble PW,Hamid Q,Elias JA

    更新日期:2001-11-15 00:00:00

  • Additional minocycline pleurodesis after thoracoscopic surgery for primary spontaneous pneumothorax.

    abstract:RATIONALE:Ipsilateral recurrence rates of spontaneous pneumothorax after video-assisted thoracoscopic surgery are higher than rates after open thoracotomy. OBJECTIVES:This study was conducted to determine whether additional minocycline pleurodesis would be effective in diminishing recurrence after video-assisted thora...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.1164/rccm.200509-1414OC

    authors: Chen JS,Hsu HH,Chen RJ,Kuo SW,Huang PM,Tsai PR,Lee JM,Lee YC

    更新日期:2006-03-01 00:00:00

  • Endothelin-1 receptor density, distribution, and function in human isolated asthmatic airways.

    abstract::The potent bronchoconstrictor and mitogenic actions of the peptide endothelin-1 (ET-1) on airway smooth muscle may contribute significantly to the bronchial obstruction observed in asthma. However, the status of the receptor-effector systems that mediate these actions of ET-1 in asthmatic airways is currently unknown....

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.152.5.7582310

    authors: Goldie RG,Henry PJ,Knott PG,Self GJ,Luttmann MA,Hay DW

    更新日期:1995-11-01 00:00:00

  • Noninvasive Ventilation Use in Critically Ill Patients with Acute Asthma Exacerbations.

    abstract::Rationale: Noninvasive ventilation decreases the need for invasive mechanical ventilation and mortality among patients with chronic obstructive pulmonary disease but has not been well studied in asthma.Objectives: To assess the association between noninvasive ventilation and subsequent need for invasive mechanical ven...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.201910-2021OC

    authors: Althoff MD,Holguin F,Yang F,Grunwald GK,Moss M,Vandivier RW,Ho PM,Kiser TH,Burnham EL

    更新日期:2020-12-01 00:00:00

  • The effect of mode, inspiratory time, and positive end-expiratory pressure on partial liquid ventilation.

    abstract::Partial liquid ventilation (PLV) has been shown to be an effective means of improving oxygenation in the injured lung. However, little is known about how approach to ventilation during PLV affects gas exchange and pulmonary mechanics. We hypothesized that gas exchange and pulmonary mechanics would be best with positiv...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.159.4.9711021

    authors: Fujino Y,Kirmse M,Hess D,Kacmarek RM

    更新日期:1999-04-01 00:00:00

  • The inflammatory role of platelets in cystic fibrosis.

    abstract::Platelets are an important, albeit generally underappreciated, component of the inflammatory cascade. Platelets are known to contribute to inflammation in atherosclerosis, stroke, and asthma. They produce a large number of proinflammatory lipid mediators and cytokines, and play a vital role in recruitment of leukocyte...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章,评审

    doi:10.1164/rccm.200508-1243PP

    authors: O'Sullivan BP,Michelson AD

    更新日期:2006-03-01 00:00:00

  • Elevated exhaled nitric oxide in newborns of atopic mothers precedes respiratory symptoms.

    abstract:RATIONALE:Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in asthma. Its role in the disease process before the onset of respiratory symptoms remains unclear. OBJECTIVES:To examine whether elevated NO in newborns with clinically naive airways is associated with subsequent respirator...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/rccm.200606-782OC

    authors: Latzin P,Kuehni CE,Baldwin DN,Roiha HL,Casaulta C,Frey U

    更新日期:2006-12-15 00:00:00

  • Maximizing the utilization of donor organs offered for lung transplantation.

    abstract::The number of patients awaiting lung transplantation (LT) and waiting time for surgery is increasing. In Australia, LT rates are 4. 6/million population/yr, which despite low organ donation rates, are the highest published in the world. The Australian organ allocation system allows identification of marginal donors an...

    journal_title:American journal of respiratory and critical care medicine

    pub_type: 杂志文章

    doi:10.1164/ajrccm.160.1.9811017

    authors: Gabbay E,Williams TJ,Griffiths AP,Macfarlane LM,Kotsimbos TC,Esmore DS,Snell GI

    更新日期:1999-07-01 00:00:00