SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Persson Daniel) ;pers:(Eklund Daniel)"

Sökning: WFRF:(Persson Daniel) > Eklund Daniel

  • Resultat 1-10 av 12
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Andersson, Henrik, et al. (författare)
  • Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages
  • 2014
  • Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 9:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response contributing to the early control of Mtb infection.
  •  
2.
  • Eklund, Daniel, 1984-, et al. (författare)
  • Vitamin D enhances IL-1β secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients
  • 2013
  • Ingår i: International journal of mycobacteriology. - Netherlands : Wolters Kluwer. - 2212-5531. ; 2:1, s. 18-25
  • Tidskriftsartikel (refereegranskat)abstract
    • The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MTB), the bacterium responsible for tuberculosis (TB), has rekindled the interest in the role of nutritional supplementation of micronutrients, such as vitamin D, as adjuvant treatment. Here, the growth of virulent MTB in macrophages obtained from the peripheral blood of patients with and without TB was studied. The H37Rv strain genetically modified to express Vibrio harveyi luciferase was used to determine the growth of MTB by luminometry in the human monocyte-derived macrophages (hMDMs) from study subjects. Determination of cytokine levels in culture supernatants was performed using a flow cytometry-based bead array technique. No differences in intracellular growth of MTB were observed between the different study groups. However, stimulation with 100nM 1,25-dihydroxyvitamin D significantly enhanced the capacity of hMDMs isolated from TB patients to control the infection. This effect was not observed in hMDMs from the other groups. The interleukin (IL)-1β and IL-10 release by hMDMs was clearly increased upon stimulation with 1,25-dihydroxyvitamin D. Furthermore, the 1,25-dihydroxyvitamin D stimulation also led to elevated levels of TNF-α (tumor necrosis factor-alpha) and IL-12p40. It was concluded that vitamin D triggers an inflammatory response in human macrophages with enhanced secretion of cytokines, as well as enhancing the capacity of hMDMs from patients with active TB to restrict mycobacterial growth.
  •  
3.
  • Hedbrant, Alexander, 1987-, et al. (författare)
  • Effects on white blood cell counts and the NLRP3 inflammasome due to dust and cobalt exposure in the hard metal industry
  • 2022
  • Ingår i: Biomarkers. - : Taylor & Francis. - 1354-750X .- 1366-5804. ; , s. 60-70
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: In light of potential negative health effects of cobalt exposure, a characterization of inflammatory mechanisms in exposed individuals is warranted. The current study investigated cobalt exposure in the Swedish hard metal industry and its relationship to inflammatory markers, including NLRP3 inflammasome activation and white blood cell (WBC) counts.MATERIAL AND METHODS: Inhalable cobalt and dust exposures, and systemic cobalt levels, were determined for 72 workers in the hard metal industry and linear regression models were applied to correlate exposure to markers of inflammasome activation and WBC counts.RESULTS: Mean exposures to inhalable dust (0.11 mg/m3) and cobalt (0.0034 mg/m3) were below the Swedish occupational exposure limits, and these low exposures did not correlate with any investigated outcomes. Instead, cobalt blood levels significantly correlated with a ca 10% decrease in IL-18 plasma levels per 10 nM cobalt increase. Furthermore, pre-shift cobalt blood and/or urine levels significantly correlated with some WBC measures, including decreased neutrophil-to-lymphocyte ratio, increased lymphocyte-to-monocyte ratio, and lymphocyte counts.CONCLUSION: The low inhalable particle exposures had no impact on WBC counts and inflammasome activation. Instead, systemic cobalt levels, which also include skin exposure, demonstrated possible suppressive effects on inflammatory responses in cobalt-exposed individuals in the hard metal industry.
  •  
4.
  • Hedbrant, Alexander, Ph.D, 1987-, et al. (författare)
  • Occupational quartz and particle exposure affect systemic levels of inflammatory markers related to inflammasome activation and cardiovascular disease
  • 2023
  • Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The inflammatory responses are central components of diseases associated with particulate matter (PM) exposure, including systemic diseases such as cardiovascular diseases (CVDs). The aim of this study was to determine if exposure to PM, including respirable dust or quartz in the iron foundry environment mediates systemic inflammatory responses, focusing on the NLRP3 inflammasome and novel or established inflammatory markers of CVDs.METHODS: The exposure to PM, including respirable dust, metals and quartz were determined in 40 foundry workers at two separate occasions per worker. In addition, blood samples were collected both pre-shift and post-shift and quantified for inflammatory markers. The respirable dust and quartz exposures were correlated to levels of inflammatory markers in blood using Pearson, Kendall τ and mixed model statistics. Analyzed inflammatory markers included: 1) general markers of inflammation, including interleukins, chemokines, acute phase proteins, and white blood cell counts, 2) novel or established inflammatory markers of CVD, such as growth/differentiation factor-15 (GDF-15), CD40 ligand, soluble suppressor of tumorigenesis 2 (sST2), intercellular/vascular adhesion molecule-1 (ICAM-1, VCAM-1), and myeloperoxidase (MPO), and 3) NLRP3 inflammasome-related markers, including interleukin (IL)-1β, IL-18, IL-1 receptor antagonist (IL-1Ra), and caspase-1 activity.RESULTS: The average respirator adjusted exposure level to respirable dust and quartz for the 40 foundry workers included in the study was 0.65 and 0.020 mg/m3, respectively. Respirable quartz exposure correlated with several NLRP3 inflammasome-related markers, including plasma levels of IL-1β and IL-18, and several caspase-1 activity measures in monocytes, demonstrating a reverse relationship. Respirable dust exposure mainly correlated with non-inflammasome related markers like CXCL8 and sST2. CONCLUSIONS: The finding that NLRP3 inflammasome-related markers correlated with PM and quartz exposure suggest that this potent inflammatory cellular mechanism indeed is affected even at current exposure levels in Swedish iron foundries. The results highlight concerns regarding the safety of current exposure limits to respirable dust and quartz, and encourage continuous efforts to reduce exposure in dust and quartz exposed industries.
  •  
5.
  • Hedbrant, Alexander, 1987-, et al. (författare)
  • Quartz Dust Exposure Affects NLRP3 Inflammasome Activation and Plasma Levels of IL-18 and IL-1Ra in Iron Foundry Workers
  • 2020
  • Ingår i: Mediators of Inflammation. - : Hindawi Publishing Corporation. - 0962-9351 .- 1466-1861.
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To study the association between inhalation of particulate matter or quartz in Swedish iron foundries and the effects on NLRP3 inflammasome activation. Methods: Particle exposure measurements were performed during an eight-hour work day for 85 foundry workers at three Swedish iron foundries. Personal sampling was used for measurement of respirable quartz and dust and stationary measurements to obtain exposure measurements for inhalable dust and PM10. The NLRP3 inflammasome markers, interleukin- (IL-) 1β and IL-18, and inhibitors IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP) were measured in plasma. Inflammasome activation was measured by caspase-1 enzymatic activity in monocytes in whole blood by flow cytometry, and expression of inflammasome-related genes was quantified using real-time PCR. Multiple linear regression analysis was used to investigate associations between PM exposures and inflammatory markers. Sex, age, smoking, current infection, BMI, and single nucleotide polymorphism in the inflammasome regulating genes CARD8 (C10X) and NLRP3 (Q705K) were included as covariates. Results: The average exposure levels of respirable dust and quartz were 0.85 and 0.052 mg/m3, respectively. A significant exposure-response was found for respirable dust and IL-18 and for inhalable dust and IL-1Ra. Whole blood, drawn from study participants, was stimulated ex vivo with inflammasome priming stimuli LPS or Pam3CSK4, resulting in a 47% and 49% increase in caspase-1 enzymatic activity in monocytes. This increase in caspase-1 activity was significantly attenuated in the higher exposure groups for most PM exposure measures. Conclusions: The results indicate that exposure levels of PM in the iron foundry environment can affect the NLRP3 inflammasome and systemic inflammation.
  •  
6.
  • Midtbö, Kristine, 1991-, et al. (författare)
  • Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1 β and Interleukin-18 from Human Monocytes
  • 2020
  • Ingår i: Mediators of Inflammation. - : Hindawi Publishing Corporation. - 0962-9351 .- 1466-1861. ; 2020
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammasomes cleave and activate interleukin- (IL-) 1β and IL-18 which have both shared and unique biological functions. IL-1β is an important mediator of the acute phase response to infections and tissue damage, whereas IL-18 takes part in activation and tailoring of the adaptive immune response. While IL-1β has served as the prototypic indicator of inflammasome activation, few studies have compared the potential differences in IL-1β and IL-18 production during inflammasome activation. Since these cytokines partake in different immune pathways, the involvement of inflammasome activity in different conditions needs to be described beyond IL-1β production alone. To address a potential heterogeneity in inflammasome functionality, ATP, chitosan, or silica oxide (SiO2) were used to induce NLRP3 inflammasome activation in THP-1 cells and the subsequent outcomes were quantified. Despite using doses of the inflammasome inducers yielding similar release of IL-1β, SiO2-stimulated cells showed a lower concentration of released IL-18 compared to ATP and chitosan. Hence, the cells stimulated with SiO2 responded with a distinctly different IL-18 : IL-1β ratio. The difference in the IL-18 : IL-1β ratio for SiO2 was constant over different doses. While all downstream responses were strictly dependent on a functional NLRP3 inflammasome, the differences did not depend on the level of gene expression, caspase-1 activity, or pyroptosis. We suggest that the NLRP3 inflammasome response should be considered a dynamic process, which can be described by taking the ratio between IL-1β and IL-18 into account and moving away from an on/off perspective of inflammasome activation.
  •  
7.
  • Nikaein, Niloofar, 1989-, et al. (författare)
  • Mathematical models disentangle the role of IL-10 feedbacks in human monocytes upon proinflammatory activation
  • 2023
  • Ingår i: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 299:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation is one of the vital mechanisms through which the immune system responds to harmful stimuli. During inflammation, pro and anti-inflammatory cytokines interplay to orchestrate fine-tuned, dynamic immune responses. The cytokine interplay governs switches in the inflammatory response and dictates the propagation and development of the inflammatory response. Molecular pathways underlying the interplay are complex, and time-resolved monitoring of mediators and cytokines is necessary as a basis to study them in detail. Our understanding can be advanced by mathematical models which enable to analyze the system of interactions and their dynamical interplay in detail. We, therefore, used a mathematical modeling approach to study the interplay between prominent pro and anti-inflammatory cytokines with a focus on tumor necrosis factor (TNF) and interleukin 10 (IL-10) in lipopolysaccharide (LPS)-primed primary human monocytes. Relevant time-resolved data were generated by experimentally adding or blocking IL-10 at different time points. The model was successfully trained and could predict independent validation data and was further used to perform simulations to disentangle the role of IL-10 feedbacks during an acute inflammatory event. We used the insight to obtain a reduced predictive model including only the necessary IL-10-mediated feedbacks. Finally, the validated reduced model was used to predict early IL-10 - TNF switches in the inflammatory response. Overall, we gained detailed insights into fine-tuning of inflammatory responses in human monocytes and present a model for further use in studying the complex and dynamic process of cytokine-regulated acute inflammation.
  •  
8.
  • Nyman, Elin, et al. (författare)
  • Mechanisms of a sustained anti-inflammatory drug response in alveolar macrophages unraveled with mathematical modeling
  • 2020
  • Ingår i: CPT. - : John Wiley & Sons. - 2163-8306. ; 9:12, s. 707-717
  • Tidskriftsartikel (refereegranskat)abstract
    • Both initiation and suppression of inflammation are hallmarks of the immune response. If not balanced, the inflammation may cause extensive tissue damage, which is associated with common diseases, e.g. asthma and atherosclerosis. Anti-inflammatory drugs come with side-effects which may be aggravated by high and fluctuating drug concentrations. To remedy this, an anti-inflammatory drug should have an appropriate pharmacokinetic half-life or better still: a sustained anti-inflammatory drug response. However, we still lack a quantitative mechanistic understanding of such sustained effects. Here, we study the anti-inflammatory response to a common glucocorticoid drug, Dexamethasone. We find a sustained response 22 hours after drug removal. With hypothesis testing using mathematical modeling, we unravel the underlying mechanism - a slow release of Dexamethasone from the receptor-drug complex. The developed model is in agreement with time-resolved training and testing data, and is used to simulate hypothetical treatment schemes. This work opens up for a more knowledge-driven drug development, to find sustained anti-inflammatory responses and fewer side effects.
  •  
9.
  • Persson, Alexander, 1978-, et al. (författare)
  • Apoptotic neutrophils activates the inflammatory response in macrophages –increased capacity to handle intracellular infection
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Inflammation is essential to eradicate invading pathogens but an uncontrolled inflammation may develop into chronic inflammation and extensive tissue destruction unable of effectively controlling infections. At the site of infection, macrophages are the major regulators of the inflammatory response through balanced release of pro- or anti-inflammatory cytokines and therefore a key cell in the resolution of inflammation. Neutrophils effectively phagocytose and kill pathogens but they are short-lived and removal of these dead cells by macrophages is a key event in the resolution of inflammation and tissue repair. However, down-regulation of the immune response by apoptotic cells would in the presence of pathogens be detrimental to the host. In contrast to resolution of inflammation, we show that in the presence of microbial stimuli, apoptotic neutrophils in fact exert a potent pro-inflammatory activation of macrophages. This augmentation of the pro-inflammatory response is dependent on uptake of the apoptotic cells by the macrophage. In addition to secretion of TNF-α, presence of apoptotic neutrophils enhanced the capacity of the stimulated macrophages to kill intracellular Mycobacterium tuberculosis. This presents a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response, and control of intracellular infections.
  •  
10.
  • Persson, Alexander, et al. (författare)
  • Induction of apoptosis in human neutrophils by Mycobacterium tuberculosis is dependent on mature bacterial lipoproteins
  • 2009
  • Ingår i: Microbial Pathogenesis. - : Elsevier BV. - 0882-4010 .- 1096-1208. ; 47:3, s. 143-150
  • Tidskriftsartikel (refereegranskat)abstract
    • Modulation of immune cell apoptosis is a key evasion strategy utilized by Mycobacterium tuberculosis (Mtb). To be able to multiply within macrophages, the bacterium delays apoptosis and down-regulates pro-inflammatory activation in these cells, whereas apoptosis is rapidly induced in the potently bactericidal neutrophils. Initial host-pathogen interactions between neutrophils and Mtb, subsequently leading to apoptosis, need to be investigated to understand the early features during Mtb infections. Opsonized Mtb were readily phagocytosed, and the immuno-mediated phagocytosis triggered early activation of anti-apoptotic Akt in the neutrophils but the bacteria still induced apoptosis to the same extent as non-phagocytosed Mtb. Mtb-induced apoptosis was strictly dependent on NADPH oxidase-generated reactive oxygen species, compounds shown to damage lysosomal granules. Despite this, we found no involvement of damaged azurophilic granules in Mtb-induced apoptosis in human neutrophils. Instead, the Mtb-induced apoptosis was p38 MAPK dependent and induced through the mitochondrial pathway. Moreover, Mtb deficient of mature lipoproteins lacked the determinants required for induction of neutrophil apoptosis. These results show that Mtb exert a strong intrinsic capacity to induce apoptosis in neutrophils that is capable of overcoming the anti-apoptotic signaling in the cell.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 12
Typ av publikation
tidskriftsartikel (10)
annan publikation (1)
konferensbidrag (1)
Typ av innehåll
refereegranskat (10)
övrigt vetenskapligt/konstnärligt (1)
populärvet., debatt m.m. (1)
Författare/redaktör
Persson, Alexander, ... (7)
Eklund, Daniel, 1984 ... (7)
Stendahl, Olle (6)
Särndahl, Eva, 1963- (5)
Lerm, Maria (4)
visa fler...
Idh, Jonna (3)
Andersson, Lena, 196 ... (3)
Paues, Jakob (3)
Persson, Hans Lennar ... (3)
Schön, Thomas (2)
Blomgran, Robert (2)
Larsson, Marie C (2)
Westberg, Håkan, 194 ... (2)
Persson, Alexander (2)
Welin, Amanda (2)
Bryngelsson, Ing-Lis ... (2)
Svensson, Kristoffer (2)
Hedbrant, Alexander, ... (2)
Fransson, Sven Göran (2)
Andersson, Henrik (1)
Engström, Christophe ... (1)
Schon, Thomas (1)
Larsson, Marie (1)
Welin, Amanda, 1983 (1)
Hedbrant, Alexander, ... (1)
Repsilber, Dirk, 197 ... (1)
Andersson, Blanka (1)
Westberg, Håkan (1)
Kruse, Robert, 1972- (1)
Ngoh, Eyler (1)
Cedersund, Gunnar (1)
Nånberg, Eewa, 1957- (1)
Fransson, Sven Göran ... (1)
Fridén, Markus (1)
Lindh, Maria (1)
Nyman, Elin (1)
Lövfors, William (1)
Bäckström, Erica (1)
Cedersund, Gunnar, A ... (1)
Simonsson, Christian (1)
Jacobson, Petra (1)
Tuerxun, Kaya, 1981- (1)
Nyman, Elin, Associa ... (1)
Midtbö, Kristine, 19 ... (1)
Nikaein, Niloofar, 1 ... (1)
Thonig, Antje (1)
Tuerxun, Kedeye (1)
Lundstrom, Charlotte (1)
visa färre...
Lärosäte
Örebro universitet (9)
Linköpings universitet (7)
Göteborgs universitet (1)
Uppsala universitet (1)
Mälardalens universitet (1)
Språk
Engelska (12)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (9)
Naturvetenskap (3)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy