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| 2. |
- Abdel-Aziz, Mahmoud I., et al.
(författare)
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A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes
- 2022
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 59:1
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Tidskriftsartikel (refereegranskat)abstract
- A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.
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| 3. |
- Lundström, Susanna L., et al.
(författare)
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Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure
- 2011
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Ingår i: PLOS ONE. - San Francisco, CA : Public Library of Science. - 1932-6203. ; 6:8, s. e23864-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.Objectives: This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.Methods: Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPAR gamma). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.Results: Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and alpha-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.Conclusions: Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.
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| 4. |
- Che, Karlhans Fru, et al.
(författare)
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The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
- 2018
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Ingår i: Clinical Science. - 0143-5221. ; 132:9, s. 959-983
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Tidskriftsartikel (refereegranskat)abstract
- Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor κ B (NF-κB); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-κB and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples ) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.
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| 5. |
- Levänen, Bettina, et al.
(författare)
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Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients.
- 2013
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 131:3, s. 894-903
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Tidskriftsartikel (refereegranskat)abstract
- 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 (Q(2) = 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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| 6. |
- Merid, Simon Kebede, et al.
(författare)
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Integration of gene expression and DNA methylation identifies epigenetically controlled modules related to PM2.5 exposure
- 2020
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Ingår i: Environment International. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 0160-4120 .- 1873-6750.
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Tidskriftsartikel (refereegranskat)abstract
- Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.
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