| 1. |
- Eldh, Maria, 1980, et al.
(författare)
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Exosomes Communicate Protective Messages during Oxidative Stress; Possible Role of Exosomal Shuttle RNA.
- 2010
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Exosomes are small extracellular nanovesicles of endocytic origin that mediate different signals between cells, by surface interactions and by shuttling functional RNA from one cell to another. Exosomes are released by many cells including mast cells, dendritic cells, macrophages, epithelial cells and tumour cells. Exosomes differ compared to their donor cells, not only in size, but also in their RNA, protein and lipid composition.
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| 2. |
- Andersson, Anders, et al.
(författare)
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Effects of Tobacco Smoke on IL-16 in CD8+ Cells from Human Airways and Blood: a Key Role for Oxygen Free Radicals?
- 2011
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Ingår i: AJP - Lung cellular and molecular physiology. - : American Physiological Society. - 1522-1504. ; 300:1
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Tidskriftsartikel (refereegranskat)abstract
- Chronic exposure to tobacco smoke leads to an increase in the frequency of infections and in CD8(+) and CD4(+)cells as well as the CD4(+) chemo-attractant cytokine IL-16 in the airways. Here, we investigated whether tobacco smoke depletes intracellular IL-16 protein and inhibits de novo production of IL-16 in CD8(+) cells from human airways and blood, while at the same time increasing extracellular IL-16 and whether oxygen free radicals (OFR) are involved. Intracellular IL-16 protein in CD8(+) cells and mRNA in all cells was decreased in bronchoalveolar lavage (BAL) samples from chronic smokers. This was also the case in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro; in which oxidized proteins were markedly increased. Extracellular IL-16 protein was increased in cell-free BAL fluid from chronic smokers and in human blood CD8(+) cells exposed to water-soluble tobacco smoke components in vitro. This was not observed in occasional smokers after short-term exposure to tobacco smoke. A marker of activation (CD69) was slightly increased whereas other markers of key cellular functions (membrane integrity, apoptosis and proliferation) in human blood CD8(+) cells in vitro were negatively affected by water-soluble tobacco smoke components. An OFR scavenger prevented these effects whereas a protein synthesis inhibitor, a beta-adrenoceptor, a glucocorticoid receptor agonist, a phosphodiesterase, a calcineurin phosphatase and a caspase-3 inhibitor did not. In conclusion, tobacco smoke depletes preformed intracellular IL-16 protein, inhibits its de novo synthesis and distorts key cellular functions in human CD8(+) cells. OFR may play a key role in this context.
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| 3. |
- Andersson, Anders, et al.
(författare)
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Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes
- 2004
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 138:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- CD4(+) and CD8(+) lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8(+) cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4(+) lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4(+) or CD8(+) lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Ralpha) protein were also measured in conditioned medium from human blood CD4(+) and CD8(+) lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription-polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Ralpha in conditioned medium from CD4(+) and CD8(+) lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8(+) cytokine IL-16, in the airway lumen, in blood CD4(+) and CD8(+) lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4(+) lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.
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| 4. |
- Andersson, Anders, et al.
(författare)
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Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD
- 2016
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Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 11, s. 2245-2258
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8(+)) and helper (CD4(+)) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4(+)-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR). Methods: We quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein. Results: The extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups. Notably, intracellular IL-16 protein was detected in all types of blood leukocytes. All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status. Further, both NK and CD4(+) T-cell concentrations displayed a negative correlation with pack-years. Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug. Conclusion: Long-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood. However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors-conditions that are over-represented among smokers.
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| 5. |
- Bossios, Apostolos, 1969, et al.
(författare)
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IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome.
- 2009
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; :Nov 26
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Tidskriftsartikel (refereegranskat)abstract
- To cite this article: Bossios A, Sjöstrand M, Dahlborn A-K, Samitas K, Malmhäll C, Gaga M, Lötvall J. IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome. Allergy 2009. DOI: 10.1111/j.1398-9995.2009.02271.x.Abstract Background: Eosinophils develop from hematopoietic CD34(+) progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34(+) cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34(+) cells can be found in situ in ongoing eosinophilic disease. Methods: CD34(+) cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg-Strauss syndrome were analyzed by flow cytometry for CD34(+)/IL-5(+) cells, and immunohistochemical staining of CD34(+)/IL-5(+) cells in bronchial biopsies from an asthmatic patient was performed. Results: Both PB and BM CD34(+) cells can produce and release IL-5 when stimulated in vitro. In the Churg-Strauss patient, IL-5-producing CD34(+) cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34(+)/IL-5(+) cells were present in a patient with asthma. Conclusion: CD34(+) cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34(+) progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases.
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| 6. |
- Cui, Zhi-Hua, 1958, et al.
(författare)
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Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways.
- 2012
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs) and thromboxane A2 (TXA2). The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA) sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2) after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187) induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.
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| 7. |
- Ekström, Karin, 1978, et al.
(författare)
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Characterization of mRNA and microRNA in human mast cell-derived exosomes and their transfer to other mast cells and blood CD34 progenitor cells
- 2012
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Ingår i: Journal of Extracellular Vesicles (JEV). - : Wiley. - 2001-3078. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exosomes are nanosized vesicles of endocytic origin that are released into the extracellular environment by many different cells. It has been shown that exosomes from various cellular origins contain a substantial amount of RNA (mainly mRNA and microRNA). More importantly, exosomes are capable of delivering their RNA content to target cells, which is a novel way of cell-to-cell communication. The aim of 20 this study was to evaluate whether exosomal shuttle RNA could play a role in the communication between human mast cells and between human mast cells and human CD34+progenitor cells. Methods: The mRNA and microRNA content of exosomes from a human mast cell line, HMC-1, was analysed by using microarray technology. Co-culture experiments followed by flow cytometry analysis and confocal microscopy as well as radioactive labeling experiments were performed to examine the uptake of 25 these exosomes and the shuttle of the RNA to other mast cells and CD34+ progenitor cells. Results: In this study, we show that human mast cells release RNA-containing exosomes, with the capacity to shuttle RNA between cells. Interestingly, by using microRNA microarray analysis, 116 microRNAs could be identified in the exosomes and 134 microRNAs in the donor mast cells. Furthermore, DNA microarray experiments revealed the presence of approximately 1800 mRNAs in the exosomes, which represent 15% of 30 the donor cell mRNA content. In addition, transfer experiments revealed that exosomes can shuttle RNA between human mast cells and to CD34+ hematopoietic progenitor cells. Conclusion: These findings suggest that exosomal shuttle RNA (esRNA) can play a role in the communication between cells, including mast cells and CD34+ progenitor cells, implying a role in cells maturation process. 35
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| 8. |
- Eldh, Maria, 1980, et al.
(författare)
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MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma
- 2014
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Ingår i: BMC Cancer. - London : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.
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| 9. |
- Glader, Pernilla, 1975, et al.
(författare)
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Impact of acute exposure to tobacco smoke on gelatinases in the bronchoalveolar space.
- 2008
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003. ; 32:3, s. 644-650
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies have indicated increased gelatinase activity in the airways of patients suffering from chronic obstructive pulmonary disease caused by tobacco smoke. The present study aimed to determine whether acute exposure to tobacco smoke per se causes a substantial and lasting impact on gelatinases and their inhibitors in the peripheral airways of atopic and nonatopic human subjects. Bronchoscopy with bronchoalveolar lavage (BAL) was performed on occasional smokers with and without atopy before and after smoking 10 cigarettes over a 48-h period. Samples from a group of never-smokers not exposed to tobacco smoke served as controls. Gelatinase identity and activity were measured using zymography, and gelatinase activity assay and concentrations of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 were measured using ELISA. The results revealed no pronounced changes in identity, net activity or concentration of the gelatinases or changes in concentrations of TIMP-1 and TIMP-2 in BAL fluid before and after acute exposure to tobacco smoke. In conclusion, the present experimental study indicates that acute exposure to tobacco smoke does not cause any substantial impact on gelatinases or their inhibitors in the peripheral airways, irrespective of atopy status, a finding that is compatible with the fact that it takes many years of tobacco smoking to establish chronic obstructive pulmonary disease.
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| 10. |
- Glader, Pernilla, 1975, et al.
(författare)
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Interleukin-17-producing T-helper cells and related cytokines in human airways exposed to endotoxin.
- 2010
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Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003. ; 36:5, s. 1155-64
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies on mouse models have indicated that interleukin (IL)-17 and IL-17-producing T-helper (Th) cells are important for pulmonary host defence against Gram-negative bacteria. Human correlates to these findings have not yet been demonstrated. The aim of the present study was to determine whether or not IL-17-producing Th cells are present and whether IL-17 and other Th17-associated cytokines are involved in the immunological response to endotoxin in human airways. Segmental exposure to endotoxin and contralateral exposure to vehicle were performed in the lungs of healthy volunteers, with subsequent bronchoalveolar lavage 12 or 24 h after exposure to study local changes in cytokines and inflammatory cells. Endotoxin exposure increased concentrations of IL-17, IL-22 and their downstream effector molecules, human β-defensin-2 and IL-8/CXC chemokine ligand 8, in bronchoalveolar lavage fluid. Th cells with the capacity to produce IL-17 were found among the bronchoalveolar lavage cells, and expression of IL-17 mRNA correlated with expression of the transcription factor, retinoic-acid-receptor-related orphan receptor C variant 2. Moreover, endotoxin increased the numbers of neutrophils, macrophages and IL-17-producing T-cells, as well as the concentration of the Th17-regulating cytokines, IL-21 and IL-23. In conclusion, IL-17-producing Th cells are present, and IL-17, as well as other Th17-associated cytokines, is involved in the immunological response to endotoxin in human airways.
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