Changes in the proteome of human bronchial epithelial cells following stimulation with leucotriene E<sub>4</sub> and transforming growth factor‐β<sub>1</sub>

Altraja, Siiri; Jaama, Juta; Valk, Ervin; Altraja, Alan

doi:10.1111/j.1440-1843.2008.01414.x

Cited by 11 publications

(7 citation statements)

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“…Interestingly, some inflammatory mediators, such as CXCL12 and TGF-β1, have been reported to be able to modify expression pattern of hnRNP A2/B1 [58], [59]. Then the influence of IRF-3 alternative splicing regulated by hnRNP A1/A2 and SF2/ASF on immunomodulatory functions of human tumor cells or immune cells justifies more extensive research.…”

Section: Discussionmentioning

confidence: 99%

HnRNP A1/A2 and SF2/ASF Regulate Alternative Splicing of Interferon Regulatory Factor-3 and Affect Immunomodulatory Functions in Human Non-Small Cell Lung Cancer Cells

Guo

Ning

et al. 2013

PLoS ONE

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Heterogeneous nuclear ribonucleoparticule A1/A2 (hnRNP A1/A2) and splicing factor 2/alternative splicing factor (SF2/ASF) are pivotal for precursor messenger RNA (pre-mRNA) splicing. Interferon regulatory factor-3 (IRF-3) plays critical roles in host defense against viral and microbial infection. Truncated IRF-3 proteins resulting from alternative splicing have been identified and characterized as functional antagonists to full-length IRF-3. In this study, we examined the molecular mechanism for splicing regulation of IRF-3 pre-mRNA and first reported the regulatory effect of hnRNP A1/A2 and SF2/ASF on IRF-3 splicing and activation. RNA interference-mediated depletion of hnRNP A1/A2 or SF2/ASF in human non-small cell lung cancer (NSCLC) cells increased exclusion of exons 2 and 3 of IRF-3 gene and reduced expression levels of IRF-3 protein and IRF-3 downstream effector molecules interferon-beta and CXCL10/IP-10. In addition, direct binding of hnRNP A1 and SF2/ASF to specific binding motifs in IRF-3 intron 1 was confirmed by RNA electrophoretic mobility shift assay. Subsequent minigene splicing assay showed that IRF-3 minigenes with mutated hnRNPA 1/A2 or SF2/ASF binding motifs increased exclusion of exons 2 and 3. Moreover, knockdown of hnRNP A1/A2 or SF2/ASF in NSCLC cells reinforced phytohemagglutinin-induced tumor necrosis factor-alpha release by peripheral blood mononuclear cells (PBMC) but suppressed that of interleukin-10 in NSCLC/PBMC co-cultures. Taken together, our results suggest that specific knockdown for hnRNP A1/A2 or SF2/ASF increase exclusion of exons 2 and 3 of IRF-3 pre-mRNA and influence immunomodulatory functions of human NSCLC cells.

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Section: Discussionmentioning

confidence: 99%

HnRNP A1/A2 and SF2/ASF Regulate Alternative Splicing of Interferon Regulatory Factor-3 and Affect Immunomodulatory Functions in Human Non-Small Cell Lung Cancer Cells

Guo

Ning

et al. 2013

PLoS ONE

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“…Specifically, the IPA KB detailed roles including collagen fibrillogenesis (dermatopontin (DPT; Q07507)), protein elongation (ribosomal protein L7, -L8, (RPL7; P18124, RPL8; P62917)) and chemotaxis (peptidylprolyl isomerase A (cyclophilin A)(PPIA; P62937)). Three of the molecules have been previously described in relation to asthma, fibrosis and inflammation, including annexin 5A (ANXA5; P08758) [25], lamin A/C (LMNA;P02545) [26,27] and PPIA [28], indicating the sensitivity of the method and clinical relevance of the samples.…”

Section: Resultsmentioning

confidence: 99%

Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment

et al. 2011

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BackgroundProteomic 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 quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions.MethodsEndobronchial biopsies were taken from untreated asthmatic patients (n = 12) and healthy controls (n = 3). Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months) and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment.ResultsMore than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo.ConclusionsProteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be identified using this approach and the expression of these features is changed by inhaled glucocorticoid treatment. Quantitative proteomics may be applied to identify mechanisms of disease that may assist in the accurate and timely diagnosis of asthma.Trial registrationClinicalTrials.gov registration NCT01378039

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“…They secrete inflammatory cytokines that initiate and ultimately aggravate host innate inflammatory responses that may cause harmful immunemediated pathologies (e.g. Yoshikawa et al, 2010) and afterwards initiate remodelling of the lung (Altraja et al, 2009). In the bronchial tree, macrophages are suspended in the mucus carpet while others lie under the layer, directly attached onto the epithelial substratum (e.g.…”

Section: Bronchial Epithelial Cells (Becs) and Bronchial Macrophages mentioning

confidence: 99%

Cellular Defences of the Lung: Comparative Perspectives

Maina¹

2012

Respiratory Diseases

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'Our lungs are highly complex organs that are exquisitely specialized for gas exchange and host defense.' Rawlins (2010) 1. Introduction General considerationsThe most important function of the lung is to acquire molecular oxygen and eliminate carbon dioxide. Except probably for the gastrointestinal system, no other organ in the body interacts with the external environment as constantly and as intimately as the respiratory system. For example, during a 24 hour period, at rest, the human lung is ventilated ~25,000 times with ~20,000 L of air (e.g. Burri, 1985; Brain, 1996), it has a respiratory surface area (RSA) of ~140 m 2 (about the size of a tennis court) which is located in the acini that lie no more than 40 to 50 cm from the external environment (air) (e.g. Weibel, 1984), and the thickness of the blood-gas (tissue) barrier (BGB) (harmonic mean thickness, ht) is 0.62 μm, a value about one-fiftieth of the thickness of a foolscap paper or that of a human head hair (Gehr et al., 1978(Gehr et al., , 1990a. By weight, each day, more than 20 kg of air enters and leaves the human body, a load that far exceeds that of food and water ingested during the same time period (Brain, 1996). Depending on the level of air pollution, different types and quantities of foreign particulates and microbial pathogens are inhaled. While large RSA and thin BGB increase gas exchange, the concomitant downside to these structural properties is that they make the lung a leading portal of entry and therefore attack by pathogenic micro-organisms, damage by allergens and particulates, and injury by noxious gases (e.g. Brain, , 1992Lambrecht et al. 2001;Garn et al., 2006). The inhaled particulates are deposited on the epithelial lining of the conducting airways and that of the peripheral air spaces where they are retained for various durations before they are removed or destroyed (e.g. Geiser et al., 1988; Gehr et al., 1990 a, b). Brain (1996) observed that 'the lung is unique in that the marriage between environment and lung disease is profound. The respiratory system threfore forms a huge challenge to the body's immune integrity (e.g. von Garnier and Nicod, 2009 , 1993;Schwartz, 1994;Brunekreef et al., 1995;Ware, 2000;Pope, 2000;Nemmar et al., 2002;Pope et al., 2002;Suwa et al., 2002;Schulz et al., 2005;Kaufman, 2010;Brook et al., 2010; van den Hooven et al., 2011;Kampfrath et al., 2011 gc.ca/ccdpc-cpcmc/crdmrc/facts_gen_e.html). According to the Canadian Lung Association (CLA), the economic burden of respiratory disease in the Country is ~3 billion ($US) dollars (http://www.bukisa.com/articles/455926_lung-health-occupational-healthincidence#ixzz1I4jwMvBX). Based on net changes in gross domestic product (GDP) growth forecasts, the estimated annual cost of SARS (Sudden Avian Respiratory Syndrome) in Asia exceeds 10 billion dollars ($US) (Lee and McKibbin, 2003;Fan, 2003;McKibbin and Sidorenko, 2006) and according to the World Bank's estimates, an influenza pandemic may result in a loss (expenditure) of 800 billion dollars ($US) (Brahm...

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Changes in the proteome of human bronchial epithelial cells following stimulation with leucotriene E₄ and transforming growth factor‐β₁

Abstract: The current findings suggest that by downregulating GR and Hsp90 alpha, CysLT may interfere with the action of glucocorticoids. Overall, the results confirm the complex role of bronchial epithelium in aspects of airway inflammation and remodelling.

Cited by 11 publications

References 49 publications

HnRNP A1/A2 and SF2/ASF Regulate Alternative Splicing of Interferon Regulatory Factor-3 and Affect Immunomodulatory Functions in Human Non-Small Cell Lung Cancer Cells

HnRNP A1/A2 and SF2/ASF Regulate Alternative Splicing of Interferon Regulatory Factor-3 and Affect Immunomodulatory Functions in Human Non-Small Cell Lung Cancer Cells

Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment

Cellular Defences of the Lung: Comparative Perspectives

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Changes in the proteome of human bronchial epithelial cells following stimulation with leucotriene E4 and transforming growth factor‐β1

Abstract: The current findings suggest that by downregulating GR and Hsp90 alpha, CysLT may interfere with the action of glucocorticoids. Overall, the results confirm the complex role of bronchial epithelium in aspects of airway inflammation and remodelling.

Cited by 11 publications

References 49 publications

HnRNP A1/A2 and SF2/ASF Regulate Alternative Splicing of Interferon Regulatory Factor-3 and Affect Immunomodulatory Functions in Human Non-Small Cell Lung Cancer Cells

HnRNP A1/A2 and SF2/ASF Regulate Alternative Splicing of Interferon Regulatory Factor-3 and Affect Immunomodulatory Functions in Human Non-Small Cell Lung Cancer Cells

Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment

Cellular Defences of the Lung: Comparative Perspectives

Contact Info

Product

Resources

About

Changes in the proteome of human bronchial epithelial cells following stimulation with leucotriene E₄ and transforming growth factor‐β₁