Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma

Paredes, Patricia Torregrosa; Esser, Julia; Admyre, Charlotte; Nord, Magnus; Rahman, Q. K.; Lukić, Ana; Rådmark, Olof; Grönneberg, R.; Grünewald, Johan; Eklúnd, Anders; Scheynius, Annika; Gabrielsson, Susanne

doi:10.1111/j.1398-9995.2012.02835.x

Cited by 167 publications

(133 citation statements)

References 37 publications

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“…In spite of the fact that miRNAs have been shown to regulate a wide variety of inflammatory processes, including chronic lung diseases such as asthma and chronic obstructive pulmonary disease, 17,29,33,57,58 no studies have previously investigated the miRNA content of exosomes isolated from BALF. In this study we demonstrated the presence of miRNAs in exosomes from BALF of both healthy subjects and asthmatic patients.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 We recently showed that exosomes from bronchoalveolar lavage fluid (BALF) of patients with asthma differ in phenotype and function compared with those from healthy subjects. 17 Furthermore, we have demonstrated that exosomes can induce cysteinyl leukotriene and IL-8 release in lung epithelial cells, an effect that was significantly higher for exosomes from asthmatic patients compared with those from healthy control subjects. 17 These findings suggest that exosomes play a role in local regulation of asthma pathology in the lung.…”

mentioning

confidence: 88%

“…17 Furthermore, we have demonstrated that exosomes can induce cysteinyl leukotriene and IL-8 release in lung epithelial cells, an effect that was significantly higher for exosomes from asthmatic patients compared with those from healthy control subjects. 17 These findings suggest that exosomes play a role in local regulation of asthma pathology in the lung.…”

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confidence: 88%

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Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients

Levänen

Bhakta

Paredes

et al. 2013

Journal of Allergy and Clinical Immunology

265

259

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Background Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge. Objective To investigate alterations in bronchoalveolar lavage fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure. Methods Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling. Results The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q2 = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles. Conclusion These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 88%

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Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients

Levänen

Bhakta

Paredes

et al. 2013

Journal of Allergy and Clinical Immunology

265

259

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“…These cells also release exosomes and other extracellular vesicles that may be involved in diverse physiological processes in airway biology and in innate (17), and adaptive (24) immune response. Previous studies reported that there is increased vesicle release by bronchial epithelial cells in cystic fibrosis patients (25), and from the lungs of asthmatic patients which induced proliferation and chemotaxis of undifferentiated monocytes (26).…”

Section: Introductionmentioning

confidence: 99%

Physical characterization and profiling of airway epithelial derived exosomes using light scattering

Kesımer

Gupta

2015

Methods

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Exosomes and other extracellular vesicles have been gaining interest during the last decade due to their emerging role in biology and, disease pathogenesis and their biomarker potential. Almost all published research related to exosomes and other extracellular vesicles include some form of physical characterization. Therefore, these vesicles should be precisely profiled and characterized physically before studying their biological role as intercellular messengers, biomarkers or therapeutic tools. Using a combination of light scattering techniques, including dynamic light scattering (DLS) and multi-angle laser light scattering combined with size exclusion separation (SEC-MALLS), we physically characterized and compared distinct extracellular vesicles derived from the apical secretions of two different cultured airway epithelial cells. The results indicated that epithelial cells release vesicles with distinct physical properties and sizes. Human primary tracheobronchial cell culture (HTBE) derived vesicles have a hydrodynamic radius (Rh) of approximately 340 nm while their radius of gyration (Rg) is approximately 200 nm. Electron microscopy analysis, however, revealed that their spherical component is 40-100 nm in size, and they carry filamentous, entangled membrane mucins on their surface that increases their overall radius. The mucin decoration on the surface defines their size and charge as measured using light scattering techniques. Their surface properties mirror the properties of the cells from which they are derived. This may provide a unique tool for researchers to elucidate the unanswered questions in normal airway biology and innate and adaptive defense, including the remodeling of airways during inflammation, tumorigenesis and metastasis.

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“…Exosomes are released by several cell types, including epithelial (Hu et al, 2013), dendritic (Segura et al, 2007), and tumor cells (Zech et al, 2012). Exosomes are also present in human body fluids such as amniotic fluid (Keller et al, 2011), urine (Chen et al, 2013), bronchoalveolar lavage fluid (Yamada et al, 2012), and malignant effusions (Torregrosa et al, 2012). It is possible that cell-derived vesicles such as exosomes could function as vectors for the intercellular transfer of molecules, thus providing a mechanism for cell-cell communication and the autologous amplification of cellular responses.…”

Section: Introductionmentioning

confidence: 99%

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

Wang¹,

Wang²,

Chen³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitor significantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.

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Bronchoalveolar lavage fluid exosomes contribute to cytokine and leukotriene production in allergic asthma

Abstract: Bronchoalveolar lavage fluid exosomes from asthmatic and healthy individuals exhibit distinct phenotypes and functions. BALF exosomes from asthmatics might contribute to subclinical inflammation by increasing cytokine and LTC(4) generation in airway epithelium.

Cited by 167 publications

References 37 publications

Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients

Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients

Physical characterization and profiling of airway epithelial derived exosomes using light scattering

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

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