| 1. |
- Cancemi, Patrizia, et al.
(författare)
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The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity : Focus on Sicilian Long-Living Individuals (LLIs)
- 2020
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant haematochemical parameters in a Sicilian population, including long-living individuals (LLIs, ≥95 years old). A cohort of 154 healthy subjects (72 men and 82 women) of different ages (age range 20-112) was recruited. The cohort was divided into five subgroups: The first group with subjects less than 40 years old, the second group ranging from 40 to 64 years old, the third group ranging from 65 to 89 years old, the fourth group ranging from 90 to 94 years old, and the fifth group with subjects more than 95 years old. A relationship was observed between LLIs and MMP-2, but not between LLIs and MMP-9. However, in the LLI group, MMP-2 and MMP-9 values were significantly correlated. Furthermore, in LLIs, we found a positive correlation of MMP-2 with the antioxidant catabolite uric acid and a negative correlation with the inflammatory marker C-reactive protein. Finally, in LLIs MMP-9 values correlated directly both with cholesterol and with low-density lipoproteins. On the whole, our data suggest that the observed increase of MMP-2 in LLIs might play a positive role in the attainment of longevity. This is the first study that shows that serum activity of MMP-2 is increased in LLIs as compared to younger subjects. As far as we are concerned, it is difficult to make wide-ranging conclusions/assumptions based on these observations in view of the relatively small sample size of LLIs. However, this is an important starting point. Larger-scale future studies will be required to clarify these findings including the link with other systemic inflammatory and antioxidant markers.
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| 2. |
- Çevik Aras, Hülya, 1975, et al.
(författare)
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Monitoring Salivary Levels of Interleukin 1 Beta (IL-1 β) and Vascular Endothelial Growth Factor (VEGF) for Two Years of Orthodontic Treatment: A Prospective Pilot Study
- 2021
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective. Vascular endothelial growth factor (VEGF) and interleukin 1 beta (IL-1β) perform functions in orthodontic tooth movement and can be measured in the saliva. This novel approach is aimed at monitoring continuous changes in IL-1β and VEGF levels in saliva during two years of orthodontic treatment. Material and Methods. Nine healthy females (15-20 years of age) with crowding requiring four premolar extractions and fixed appliances in both jaws were included in this prospective pilot study. A total of 134 stimulated and 134 unstimulated saliva samples were collected during two years of treatment: before tooth extractions (baseline) and then every 6-8 weeks at follow-up appointments. All saliva samples were analysed by the enzyme-linked immunosorbent assay. The mean levels of IL-1β and VEGF were calculated according to the different orthodontic treatment stages: alignment, space closure, and finishing. Repeated analysis of variance (ANOVA) measurements were used to compare the means between different treatment stages. The percentage difference in IL-1β and VEGF between the different treatment stages was analysed by Bland-Altman plots. Results. A gradual increase in IL-1β and VEGF was observed at alignment, reaching significance at space closure (p=0.002 and p=0.025, respectively). At finishing, both IL-1β and VEGF declined, however, without reverting to baseline values (p=0.172 and p=0.207, respectively). Bland-Altman analysis showed the agreement between IL-1β and VEGF in terms of a systematic increase, with a higher percentage difference for VEGF. Conclusions. The salivary levels of both IL-1β and VEGF increased following orthodontic treatment and reached their peaks during the treatment stage of space closure. This novel approach provides a hint on how and when to sample saliva during orthodontic treatment to analyse bone remodelling. © 2021 Hülya Çevik-Aras et al.
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| 3. |
- Fang, Qinghua, et al.
(författare)
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Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis
- 2020
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Ingår i: Mediators of Inflammation. - : Hindawi Limited. - 0962-9351 .- 1466-1861. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis is a chronic autoimmune syndrome associated with several genetic, epigenetic, and environmental factors affecting the articular joints contributing to cartilage and bone damage. Although etiology of this disease is not clear, several immune pathways, involving immune (T cells, B cells, dendritic cells, macrophages, and neutrophils) and nonimmune (fibroblasts and chondrocytes) cells, participate in the secretion of many proinflammatory cytokines, chemokines, proteases (MMPs, ADAMTS), and other matrix lysing enzymes that could disturb the immune balance leading to cartilage and bone damage. The presence of autoantibodies preceding the clinical onset of arthritis and the induction of bone erosion early in the disease course clearly suggest that initiation events damaging the cartilage and bone start very early during the autoimmune phase of the arthritis development. During this process, several signaling molecules (RANKL-RANK, NF-κB, MAPK, NFATc1, and Src kinase) are activated in the osteoclasts, cells responsible for bone resorption. Hence, comprehensive knowledge on pathogenesis is a prerequisite for prevention and development of targeted clinical treatment for RA patients that can restore the immune balance improving clinical therapy.
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| 4. |
- Hedbrant, Alexander, 1987-, et al.
(författare)
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Quartz Dust Exposure Affects NLRP3 Inflammasome Activation and Plasma Levels of IL-18 and IL-1Ra in Iron Foundry Workers
- 2020
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Ingår i: Mediators of Inflammation. - : Hindawi Publishing Corporation. - 0962-9351 .- 1466-1861.
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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.
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| 5. |
- Jaroszynski, A, et al.
(författare)
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Heat Shock Protein 27 Levels Predict Myocardial Inhomogeneities in Hemodialysis Patients
- 2022
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Ingår i: Mediators of inflammation. - : Hindawi Limited. - 1466-1861 .- 0962-9351. ; 2022, s. 5618867-
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Tidskriftsartikel (refereegranskat)abstract
- Background. Sudden cardiac death (SCD) is the single major cause of death in hemodialysis (HD) patients. QRS-T angle is an established marker of global repolarization heterogeneity associated with electrical instability and SCD. Heat shock protein 27 (HSP27) plays an important, protective role against noxious factors in the cardiovascular (CV) system. This study is aimed at assessing whether low HSP27 is associated with myocardial inhomogeneities in HD patients, as expressed by increases in the spatial QRS-T angle. Methods. Clinical data and biochemical, echocardiographic, and electrocardiographic parameters were evaluated in 182 HD patients. Patients were split into normal and abnormal QRS-T angle groups. Results. Patients with abnormally high QRS-T angles were older and had higher prevalence of diabetes as well as myocardial infarction, higher left ventricular mass index (LVMI) and C-reactive protein, worse oxidant/antioxidant status, and lower ejection fraction and HSP27. Multiple regression analysis revealed that abnormal QRS-T values were independently, negatively associated with serum HSP27 and positively associated with LVMI. Conclusions. Low HSP27 levels are associated with increased heterogeneity of myocardial action potential, as expressed by increased spatial QRS-T angle.
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| 6. |
- Ljungberg, Liza, 1980-, et al.
(författare)
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Global Transcriptional Profiling Reveals Novel Autocrine Functions of Interleukin 6 in Human Vascular Endothelial Cells
- 2020
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Ingår i: Mediators of Inflammation. - : Hindawi Publishing Corporation. - 0962-9351 .- 1466-1861. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interleukin 6 (IL6) is a multifunctional cytokine produced by various cells, including vascular endothelial cells. IL6 has both pro- and non-/anti-inflammatory functions, and the response to IL6 is dependent on whether it acts via the membrane-bound IL6 receptor alpha (IL6R alpha) (classic signaling) or the soluble form of the receptor (transsignaling). As human endothelial cells produce IL6 and at the same time express IL6R alpha, we hypothesized that IL6 may have autocrine functions.Methods: Knockdown of IL6 in cultured human endothelial cells was performed using siRNA. Knockdown efficiency was evaluated using ELISA. RNA sequencing was employed to characterize the transcriptional consequence of IL6 knockdown, and Ingenuity Pathway Analysis was used to further explore the functional roles of IL6.Results: Knockdown of IL6 in cultured endothelial cells resulted in a 84-92% reduction in the release of IL6. Knockdown of IL6 resulted in dramatic changes in transcriptional pattern; knockdown of IL6 in the absence of soluble IL6R alpha (sIL6R alpha) led to differential regulation of 1915 genes, and knockdown of IL6 in the presence of sIL6R alpha led to differential regulation of 1967 genes (fold change 1.5, false discovery rate<0.05). Pathway analysis revealed that the autocrine functions of IL6 in human endothelial cells are mainly related to basal cellular functions such as regulation of cell cycle, signaling, and cellular movement. Furthermore, we found that knockdown of IL6 activates functions related to adhesion, binding, and interaction of endothelial cells, which seem to be mediated mainly via STAT3.Conclusion: In this study, a large number of novel genes that are under autocrine regulation by IL6 in human endothelial cells were identified. Overall, our data indicate that IL6 acts in an autocrine manner to regulate basal cellular functions, such as cell cycle regulation, signaling, and cellular movement, and suggests that the autocrine functions of IL6 in human endothelial cells are mediated via IL6 classic signaling.
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| 7. |
- Midtbö, Kristine, 1991-, et al.
(författare)
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Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1 β and Interleukin-18 from Human Monocytes
- 2020
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Ingår i: Mediators of Inflammation. - : Hindawi Publishing Corporation. - 0962-9351 .- 1466-1861. ; 2020
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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.
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