| 1. |
- Berlin, Frida
(författare)
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Mast Cell-Mediated Orchestration of Airway Epithelial Responses in Chronic Respiratory Diseases
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic respiratory diseases, such as asthma, are an increasing health issue worldwide and cause about 3.9 million deaths annually. Despite this, little is know about the molecular mechanisms underpinning disease pathogenesis. Bronchial and alveolar remodeling and impaired epithelial function are typical characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells, positive for the serine proteases; tryptase and chymase, infiltrate the epithelium and the alveolarparenchyma. While it is likely that the epithelial cells are exposed to various amounts of released tryptase and chymase, the interaction between mast cells and epithelial cells remains unknown. This thesis aimed to investigate the impact of mast cell proteases on bronchial and alveolar remodelling. Human bronchial and alveolar epithelial cells were treated with tryptase and chymase. Holographic live cell imaging, fluorescent microscopy, and gene and protein assays were used to analyze various parameters such as proliferation patterns, protein expressions and distributions. The results showed that both tryptase and chymase promoted epithelial remodelling in several ways. Tryptase induced cell growth, cell survival, and wound healing, whereas chymase reduced cell growth, altered cell morphology and impaired epithelial barrier properties. In conclusion, our results suggest that intraepithelial and alveolar mast cell release of proteases plays a crucial role in epithelial homeostasis, and that an imbalance of the protease release may be involved in respiratory disease progression and in disruption of critical epithelial functions.
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| 2. |
- Berlin, Frida, et al.
(författare)
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Mast Cell Proteases Tryptase and Chymase Induce Migratory and Morphological Alterations in Bronchial Epithelial Cells
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 22:10
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Tidskriftsartikel (refereegranskat)abstract
- Chronic respiratory diseases are often characterized by impaired epithelial function and remodeling. Mast cells (MCs) are known to home into the epithelium in respiratory diseases, but the MC-epithelial interactions remain less understood. Therefore, this study aimed to investigate the effect of MC proteases on bronchial epithelial morphology and function. Bronchial epithelial cells were stimulated with MC tryptase and/or chymase. Morphology and epithelial function were performed using cell tracking analysis and holographic live-cell imaging. Samples were also analyzed for motility-associated gene expression. Immunocytochemistry was performed to compare cytoskeletal arrangement. Stimulated cells showed strong alterations on gene, protein and functional levels in several parameters important for maintaining epithelial function. The most significant increases were found in cell motility, cellular speed and cell elongation compared to non-stimulated cells. Also, cell morphology was significantly altered in chymase treated compared to non-stimulated cells. In the current study, we show that MC proteases can induce cell migration and morphological and proliferative alterations in epithelial cells. Thus, our data imply that MC release of proteases may play a critical role in airway epithelial remodeling and disruption of epithelial function.
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| 3. |
- Berlin, Frida, et al.
(författare)
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Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells
- 2023
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Ingår i: Cells. - 2073-4409. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Bronchial and alveolar remodeling and impaired epithelial function are characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells (MCs) positive for serine proteases, tryptase and chymase, infiltrate the epithelium and alveolar parenchyma. However, little is known regarding the implication of intraepithelial MCs on the local environment, such as epithelial cell function and properties. In this study, we investigated whether MC tryptase is involved in bronchial and alveolar remodeling and the mechanisms of regulation during inflammation. Using novel holographic live cell imaging, we found that MC tryptase enhanced human bronchial and alveolar epithelial cell growth and shortened the cell division intervals. The elevated cell growth induced by tryptase remained in a pro-inflammatory state. Tryptase also increased the expression of the anti-apoptotic protein BIRC3, as well as growth factor release in epithelial cells. Thus, our data imply that the intraepithelial and alveolar MC release of tryptase may play a critical role in disturbing bronchial epithelial and alveolar homeostasis by altering cell growth–death regulation.
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| 4. |
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| 5. |
- Berlin, Marie, et al.
(författare)
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Dental health care utilization among young adults who were in societal out-of-home care as children : a Swedish national cohort study
- 2018
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Ingår i: International Journal of Social Welfare. - : John Wiley & Sons. - 1369-6866 .- 1468-2397. ; 27:4, s. 325-336
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Tidskriftsartikel (refereegranskat)abstract
- We used Swedish national registers to analyse dental health care among young adults with childhood experience of out‐of‐home care (OHC), in Cox regression analyses. All 1.7 million Swedish residents born in 1980–1994 were included, of whom 4% had been in OHC. The population was followed up in the Dental Health Register from age 20 to 29, during the period 2009–2014. We found that persons with short or long OHC experience made emergency dental care visits more often than their majority‐population peers: 17–23% versus 9–10%, (adjusted Hazard ratios [HR:s] 1.60–2.02); they more often had tooth extractions, 9–12% versus 3% (HR:s 2.33–3.03); but less regularly visited a dentist for planned check‐ups, 61–77% versus 80–87% (HR:s 0.76–0.78). Since dental health in young adulthood reflects dental health and dental care in childhood, the findings of this study call for improved preventive dental health care for children in OHC.
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| 6. |
- Brunklaus, Birgit, 1970-, et al.
(författare)
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The value of assessing multiple perspectives and transdisciplinary approaches in the transition to a bio-based economy : The prospect for transforming mixed food waste into bio-based chemicals
- 2017
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Ingår i: Life Cycle Management Conference. - Luxemburg : Luxembourg Institute of Science and Technology (LIST).
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Konferensbidrag (refereegranskat)abstract
- In line with current political and industrial ambitions for a transition into a bio-based economy, food waste can be an alternative to agro- and forest-based resources. The amount of food waste generated every year is about 1.3 billion tons globally. The vast amounts cause problems related to climate change and resource depletion, as well as economic challenges related to waste disposal. These problems could be solved by transforming food waste into valuable products like bio-based chemicals. Succinic acid (SA) is one such chemical with high market potential in its bio-based version. It is already produced commercially based on cultivated biomass. Several initiatives also exist to examine the use of food waste as feedstock for SA production. Most of these initiatives are limited to homogenous industrial waste streams, but a research project in Sweden is looking also at mixed food waste (MFW) as an alternative feedstock.The purpose of this project is to evaluate the prospect for transforming mixed food waste into bio-based chemicals, such as SA. As the prospect depends on many factors, the examination is addressed with multiple perspectives: Technical and social system structures are explored, in addition to resource- and environmental implications. Several methods are thus involved in the different types of evaluations, such as the technical evaluation (including laboratory cultivation tests, and mechanical property testing), the social evaluation (including actors analysis, policy analysis, market analysis, and societal acceptance), the resources evaluation (including waste flow analysis and material flow analysis), and the environmental evaluation (including life cycle assessment of current and future valorization techniques for mixed food waste).The project uses a transdisciplinary approach and offers as such an arena where both research partners and industrial partners meet and discuss possible options for MFW-based SA production in Sweden. Here we present the results of one possible production route, where microbial production of SA from MFW in Sweden is used as a case study.Results of the case study show that even though, from a technical and resource system perspective, production seems possible, from a social system perspective it lacks institutional support and actor commitment and alignment for realizing development in Sweden. From an environmental and life cycle perspective, the framing of the question is decisive for the results: SA production from MFW is environmentally beneficial if compared with the SA production from corn, but from a pure waste handling perspective, it is environmentally better to produce biogas than SA from MFW.The findings thus indicate that different perspectives and different methods contribute with a useful holistic perspective to the evaluation. The case study is not providing a definite answer on whether the prospects for transforming MFW into bio-based chemicals are favorable or not, but gives a nuanced evaluation that offers a more firm foundation for decision than one perspective or method in isolation. The transdisciplinary approach can inform an arena of research and industrial partners with different perspectives to facilitate discussion and more well-informed decisions. The case clearly illustrates that an efficient and sustainable transition to a bio-based economy is supported by assessing multiple perspectives and applying a transdisciplinary approach.
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| 7. |
- Brunklaus, Birgit, 1970-, et al.
(författare)
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The value of transdisciplinary perspectives duringtransition to a bio-based economy : The prospect for converting mixed food wasteinto bio-based chemicals
- 2018
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Ingår i: Designing Sustainable Technologies, Products andPolicies. - Cham : Spinger. - 9783319669809 - 9783319669816 ; , s. 327-335
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Within the current political and industrial transition to a bio-basedeconomy, food waste can be an alternative resource for biobased chemicals. Thischapter describes a case study that evaluates the prospect for Swedish production ofbiobased chemicals such as succinic acid from food waste. The evaluation isaddressed from multiple systems perspectives. From a technical and resourcesystem perspective, the results of the case study show that production seems possible.However, from a social system perspective succinic acid production currentlylacks institutional support and actor commitment and alignment for realizingdevelopment in Sweden. From an environmental and life cycle perspective, thescoping of the analysis is decisive for the results. The study shows that multipleperspectives complement each other when seeking a nuanced evaluation of technicalinnovation and give insights for the intended value chain.
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| 8. |
- Callesen, Katrine T., et al.
(författare)
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Characterization of Mast Cells from Healthy and Varicose Human Saphenous Vein
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells (MCs) are distributed in tissues throughout the body and are highly involved in many physiological and pathophysiological processes. The potential and involvement of different MC phenotypes are still not well understood. MCs are present in blood vessel walls, but their specific phenotypic features are unknown. We aimed at characterizing MCs from human saphenous veins for localization, mediator content, and receptor expression. This was done in MCs from both healthy and varicose human saphenous veins (hSV and vSV, respectively). For both vSV and hSV, we found that vein MCs are mainly present in the tunica adventitia (99% MCs in adventitia) and that the population consists of both MCT and MCTC phenotypes (vSV: 55% MCT, hSV: 64% MCT). The vein MCs contained high levels of histamine (vSV: 27 pg/MC, hSV: 55 pg/MC) and tryptase (vSV: 98 pg/MC, hSV: 111 pg/MC), indicating a strong potential for regulatory effects on blood vessels. The receptor expression of FcɛRI, MRGPRX2, PTAFR, C3aR, and C5aR was found, even though the percentage of positive cells differed between vSV and hSV MCs. We conclude that vein MCs from the blood vessel wall have a high potential to affect the tissue around them.
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| 9. |
- Garcia-Ryde, Martin, et al.
(författare)
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Expression of Stress-Induced Genes in Bronchoalveolar Lavage Cells and Lung Fibroblasts from Healthy and COPD Subjects
- 2024
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Ingår i: International Journal of Molecular Sciences. - 1422-0067. ; 25:12, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is commonly caused from smoking cigarettes that induce biological stress responses. Previously we found disorganized endoplasmic reticulum (ER) in fibroblasts from COPD with different responses to chemical stressors compared to healthy subjects. Here, we aimed to investigate differences in stress-related gene expressions within lung cells from COPD and healthy subjects. Bronchoalveolar lavage (BAL) cells were collected from seven COPD and 35 healthy subjects. Lung fibroblasts were derived from 19 COPD and 24 healthy subjects and exposed to cigarette smoke extract (CSE). Gene and protein expression and cell proliferation were investigated. Compared to healthy subjects, we found lower gene expression of CHOP in lung fibroblasts from COPD subjects. Exposure to CSE caused inhibition of lung fibroblast proliferation in both groups, though the changes in ER stress-related gene expressions (ATF6, IRE1, PERK, ATF4, CHOP, BCL2L1) and genes relating to proteasomal subunits mostly occurred in healthy lung fibroblasts. No differences were found in BAL cells. In this study, we have found that lung fibroblasts from COPD subjects have an atypical ER stress gene response to CSE, particularly in genes related to apoptosis. This difference in response to CSE may be a contributing factor to COPD progression.
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| 10. |
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