Abstract:
BACKGROUND:Azithromycin (Azm) is a macrolide recognized for its disease-modifying effects and reduction in exacerbation of chronic airway diseases. It is not clear whether the beneficial effects of Azm are due to its anti-microbial activity or other pharmacological actions. We have shown that Azm affects the integrity of the bronchial epithelial barrier measured by increased transepithelial electrical resistance. To better understand these effects of Azm on bronchial epithelia we have investigated global changes in gene expression. METHODS:VA10 bronchial epithelial cells were treated with Azm and cultivated in air-liquid interface conditions for up to 22 days. RNA was isolated at days 4, 10 and 22 and analyzed using high-throughput RNA sequencing. qPCR and immunostaining were used to confirm key findings from bioinformatic analyses. Detailed assessment of cellular changes was done using microscopy, followed by characterization of the lipidomic profiles of the multivesicular bodies present. RESULTS:Bioinformatic analysis revealed that after 10 days of treatment genes encoding effectors of sterol and cholesterol metabolism were prominent. Interestingly, expression of genes associated with epidermal barrier differentiation, KRT1, CRNN, SPINK5 and DSG1, increased significantly at day 22. Together with immunostaining, these results suggest an epidermal differentiation pattern. We also found that Azm induced the formation of multivesicular and lamellar bodies in two different airway epithelial cell lines. Lipidomic analysis revealed that Azm was entrapped in multivesicular bodies linked to different types of lipids, most notably palmitate and stearate. Furthermore, targeted analysis of lipid species showed accumulation of phosphatidylcholines, as well as ceramide derivatives. CONCLUSIONS:Taken together, we demonstrate how Azm might confer its barrier enhancing effects, via activation of epidermal characteristics and changes to intracellular lipid dynamics. These effects of Azm could explain the unexpected clinical benefit observed during Azm-treatment of patients with various lung diseases affecting barrier function.
journal_name
Respir Resjournal_title
Respiratory researchauthors
Arason AJ,Joelsson JP,Valdimarsdottir B,Sigurdsson S,Gudjonsson A,Halldorsson S,Johannsson F,Rolfsson O,Lehmann F,Ingthorsson S,Cherek P,Gudmundsson GH,Gardarsson FR,Page CP,Baldursson O,Gudjonsson T,Kricker JAdoi
10.1186/s12931-019-1101-3subject
Has Abstractpub_date
2019-06-24 00:00:00pages
129issue
1eissn
1465-9921issn
1465-993Xpii
10.1186/s12931-019-1101-3journal_volume
20pub_type
杂志文章abstract:BACKGROUND:During a lipopolysaccharide-induced lung inflammation, a massive accumulation of neutrophils occurs, which is normally cleared by macrophage phagocytosis following neutrophil apoptosis. However, in cases of extensive apoptosis the normal clearance system may fail, resulting in extensive neutrophil secondary ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-143
更新日期:2006-12-14 00:00:00
abstract:BACKGROUND:Patients with severe, uncontrolled asthma, particularly those with a non-eosinophilic phenotype, have a great unmet need for new treatments that act on a broad range of inflammatory pathways in the airway. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01513-x
更新日期:2020-10-13 00:00:00
abstract:BACKGROUND:Surfactant protein D (SP-D) and Mannose Binding Lectin (MBL) are collectins that have opsonic and immunoregulatory functions, are found in lung fluid and interact with the human immunodeficiency virus (HIV). We compared collectin levels in lung fluid and serum from HIV infected and normal subjects to determi...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-42
更新日期:2007-06-13 00:00:00
abstract:BACKGROUND:To compare the efficacy and safety of budesonide/formoterol (Symbicort) with formoterol (Oxis) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting beta2-agonist therapy. METHODS:In a 3 hour, randomized, double-blind study, a total of 115 patients with acute a...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-7-13
更新日期:2006-01-24 00:00:00
abstract:BACKGROUND:The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination of in vivo and ex vivo ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0394-8
更新日期:2016-07-05 00:00:00
abstract:BACKGROUND:Patients with severe uncontrolled asthma may receive oral corticosteroid (OCS) treatment regularly. The present study investigated the health care resource utilization and cost in regularly OCS treated Swedish asthma patients. METHODS:Primary care medical records data were linked to data from Swedish nation...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0855-3
更新日期:2018-09-03 00:00:00
abstract:BACKGROUND:The relationship between the Epworth sleepiness scale (ESS) and the apnea-hypopnea index (AHI) is uncertain and even poor. The major problem associated with the ESS might be a lack of consideration of weight in prediction in clinical practice. Would awarding different item-scores to the four scales of ESS it...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01417-w
更新日期:2020-06-12 00:00:00
abstract:BACKGROUND:The mechanisms during the initial phase of oxygen toxicity leading to pulmonary tissue damage are incompletely known. Increase of tumour necrosis factor alpha (TNFalpha) represents one of the first pulmonary responses to hyperoxia. We hypothesised that, in the initial phase of hyperoxia, TNFalpha activates t...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-10
更新日期:2005-01-21 00:00:00
abstract:BACKGROUND:Few longitudinal studies examine inflammation and lung function in asthma. We sought to determine the cytokines that reduce airflow, and the influence of respiratory viral infections on these relationships. METHODS:Children underwent home collections of nasal lavage during scheduled surveillance periods and...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-018-0922-9
更新日期:2018-11-21 00:00:00
abstract::Interleukin (IL)-17 is recognized to play a critical role in numerous immune and inflammatory responses by regulating the expression of various inflammatory mediators, which include cytokines, chemokines, and adhesion molecules. There is growing evidence that IL-17 is involved in the pathogenesis of asthma. IL-17 orch...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/1465-9921-11-78
更新日期:2010-06-16 00:00:00
abstract:BACKGROUND:Pleural effusion (PE) can be divided into benign pleural effusion (BPE) and malignant pleural effusion (MPE). There is no consensus on the identification of lung cancer-associated MPE using the optimal cut-off levels from five common tumor biomarkers (CEA, CYFRA 21-1, CA125, SCC-Ag, and NSE). Therefore, we a...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01557-z
更新日期:2020-10-29 00:00:00
abstract:BACKGROUND:A multitude of epidemiological studies have shown that ambient fine particulate matter 2.5 (diameter < 2.5um; PM2.5) was associated with increased morbidity and mortality of chronic obstructive pulmonary disease (COPD). However, the underlying associated mechanisms have not yet been elucidated. We conducted ...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-019-1081-3
更新日期:2019-06-13 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr63
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia. METHODS:C57BL/6 mice received daily, nose-...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-13-40
更新日期:2012-05-31 00:00:00
abstract:BACKGROUND:Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in ast...
journal_title:Respiratory research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/1465-9921-12-160
更新日期:2011-12-21 00:00:00
abstract:BACKGROUND:Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantita...
journal_title:Respiratory research
pub_type: 杂志文章,随机对照试验
doi:10.1186/1465-9921-12-124
更新日期:2011-09-22 00:00:00
abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogene...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-7-64
更新日期:2006-04-10 00:00:00
abstract:BACKGROUND:We have previously shown that vitamin D deficiency has a detrimental impact on lung development. In this study, we aimed to identify the mechanisms linking vitamin D with lung development using a mouse model of dietary manipulation. METHODS:Female offspring were euthanized at different time-points; embryoni...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-016-0362-3
更新日期:2016-04-27 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-9-36
更新日期:2008-04-25 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-014-0161-7
更新日期:2015-01-09 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-8-62
更新日期:2007-09-06 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-12-58
更新日期:2011-04-27 00:00:00
abstract::In many model systems, cystic fibrosis (CF) phenotype airway epithelial cells in culture respond to P. aeruginosa with greater interleukin (IL)-8 and IL-6 secretion than matched controls. In order to test whether this excess inflammatory response results from the reported increased adherence of P. aeruginosa to the CF...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-69
更新日期:2005-07-11 00:00:00
abstract::There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease...
journal_title:Respiratory research
pub_type: 杂志文章,评审
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更新日期:2019-07-08 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-6-41
更新日期:2005-05-09 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-1318-1
更新日期:2020-02-18 00:00:00
abstract::Mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a protein with anti-inflammatory properties and the archetypal member of the dual-specificity phosphatases (DUSPs) family that have emerged over the past decade as playing an instrumental role in the regulation of airway inflammation. Not only does MKP-1...
journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/s12931-017-0637-3
更新日期:2017-08-10 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/1465-9921-11-83
更新日期:2010-06-22 00:00:00
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journal_title:Respiratory research
pub_type: 杂志文章,评审
doi:10.1186/rr177
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the anti...
journal_title:Respiratory research
pub_type: 杂志文章
doi:10.1186/s12931-020-01582-y
更新日期:2020-11-30 00:00:00