| 1. |
- Almroth, Gabriel, et al.
(författare)
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Sclerostin, TNF-alpha and Interleukin-18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients
- 2016
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Ingår i: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 83:1, s. 58-63
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNF-alpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.
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| 2. |
- Khalaf, Hazem, 1981-, et al.
(författare)
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Cytokines and chemokines are differentially expressed in patients with periodontitis : Possible role for TGF-beta 1 as a marker for disease progression
- 2014
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Ingår i: Cytokine. - London : Academic Press. - 1043-4666 .- 1096-0023. ; 67:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Periodontitis is a chronic inflammatory disease characterized by destruction of periodontal tissue ultimately leading to bone destruction and has been associated with other inflammatory diseases, such as atherosclerosis. Attachment loss of periodontal tissue is primarily caused by host cell-derived immune responses against subgingival biofilm. The aim of the present study was to determine the cytokine profile in serum, saliva and gingival crevicular fluid (GCF) patients with periodontitis and healthy controls. We show that periodontitis patients exhibit higher numbers of periodontal pathogens and their immune responses are significantly altered. The levels of IL-6 in saliva and GCF were significantly suppressed, and while CXCL8 was not altered in serum, its expression levels were significantly suppressed in saliva and elevated in GCF. The T-cell-derived cytokine IL-2 did not differ between patients and controls in serum and saliva, but there was a significant suppression in GCF of patients. Interestingly, TGF-beta(1) levels were significantly elevated in serum, saliva and GCF in patients compared to controls. Furthermore, by using cultured gingival fibroblasts stimulated with wild type and proteinase mutant strains of Porphyromonas gingivalis, we show that the suppression of CXCL8 and IL-6, and the induction of TGF-beta(1) is primarily mediated by the proteolytic activity of lysine-specific proteinases. These results indicate that P. gingivalis is a major contributor to the altered immune responses and the pathology of periodontitis. Furthermore, the ease of sampling and analyzing cytokine expression profiles, including TGF-beta(1), in saliva and GCF may serve to predict the progression of periodontitis and associated systemic inflammatory diseases.
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| 3. |
- Ljunggren, Stefan, 1988-, et al.
(författare)
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Modified lipoproteins in periodontitis : a link to cardiovascular disease?
- 2019
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Ingår i: Bioscience Reports. - : Portland Press. - 0144-8463 .- 1573-4935. ; 39:3
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Tidskriftsartikel (refereegranskat)abstract
- There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesize that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, this study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient-ultracentrifugation. Proteins were separated by two-dimensional gel-electrophoresis and identified by map-matching or by nano-liquid chromatography followed by mass spectrometry. ApoA-I methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed.Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of alpha-1-antichymotrypsin, apoA-II, apoC-III were found in HDL from the patients. In LDL/VLDL, the levels of apoL-1 and platelet-activating factor acetylhydrolase as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. Alpha-1 antitrypsin and alpha-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2.Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as posttranslational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).
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| 4. |
- Lönn, Johanna, 1982-, et al.
(författare)
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An Antithrombin III product containing biologically active hepatocyte growth factor may be beneficial in deep ulcer infections
- 2012
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Ingår i: Cytokine. - : Academic Press. - 1043-4666 .- 1096-0023. ; 60:2, s. 478-486
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Tidskriftsartikel (refereegranskat)abstract
- Background: Widely studied for the past 20 years, hepatocyte growth factor (HGF) has been identified as a regenerative marker and an important factor in the development and healing of injuries. Antithrombin III (AT III) is a protein in the blood stream with anti-thrombotic and anti-inflammatory properties and has been used as an adjuvant treatment along with antibiotics in severe sepsis.Objective: To study the content and properties of HGF in plasma-derived AT III products, and the regenerative effect in severe deep ulcer infections.Methods: Commercial AT III products were analyzed for the presence and biological activity of HGF. One AT III product containing biologically active HGF was used to treat 18 cases of critical, deep ulcer infections scheduled for major invasive intervention. The patients were followed up for 6-60 months.Results: The AT III products contained HGF with different biological activity. No adverse reactions were observed after local administration of AT III during the study or follow-up period. In 16 of 18 cases no surgical intervention was needed within the first 6 month of inclusion.Conclusion: AT III products containing biologically active HGF may contribute to regeneration and healing in severe deep ulcer infections which do not respond adequately to different combinations of antibiotics alone. (C) 2012 Elsevier Ltd. All rights reserved.
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| 5. |
- Lönn, Johanna, 1982-, et al.
(författare)
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Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition
- 2012
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Ingår i: Results in Immunology. - : Elsevier BV. - 2211-2839. ; 2, s. 7-12
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.
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| 6. |
- Lönn, Johanna, 1982-, et al.
(författare)
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High Concentration but Low Activity of Hepatocyte Growth Factor in Periodontitis
- 2014
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Ingår i: Journal of Periodontology. - Chicago, USA : American Academy of Periodontology. - 0022-3492 .- 1943-3670. ; 85:1, s. 113-122
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Tidskriftsartikel (refereegranskat)abstract
- Background: High levels of hepatocyte growth factor (HGF), a healing factor with regenerative and cytoprotective effects, are associated with inflammatory diseases, including periodontitis. HGF biological activity requires binding to its receptors, the proto-oncogene c-Met (c-Met) and heparan sulphate proteoglycan (HSPG). Here we investigated HGF expression and its relationship to subgingival microbiota in medically healthy individuals with and without periodontitis.Methods: Saliva, gingival crevicular fluid (GCF), and blood samples from 30 patients with severe periodontitis and 30 healthy controls were analyzed for HGF concentration using enzyme-linked immunosorbent assay (ELISA), and binding affinity for HSPG and c-Met using surface plasmon resonance (SPR). The regenerative effects of saliva from three patients and controls were analyzed in an in vitro model of cell injury. Subgingival plaques were analyzed for the presence of 18 bacterial species.Results: Patients with periodontitis showed higher HGF concentrations in saliva, GCF, and serum (P < 0.001); however, the binding affinities for HSPG and c-Met were reduced in GCF and saliva (P < 0.002). In contrast to the controls, saliva from patients showed no significant regenerative effect over time on gingival epithelial cells. Compared to controls, patients had a higher prevalence of periodontal-related bacteria.Conclusion: Higher circulatory HGF levels indicate a systemic effect of periodontitis. However, the HGF biological activity at local inflammation sites was reduced, and this effect was associated with the amount of periodontal bacteria. Loss of function of healing factors may be an important mechanism in degenerative processes in periodontally susceptible individuals.
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| 7. |
- Lönn, Johanna, 1982-, et al.
(författare)
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High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure
- 2012
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Ingår i: Advances in Bioscience and Biotechnology. - Irvine, USA : Scientific Research Publishing. - 2156-8456 .- 2156-8502. ; 3:4, s. 516-523
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS-PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for development of CRF we aimed to assess the amounts and affinity of HGF in this patient group. Elisa, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P < 0.0001), but decreased affinity to HSPG (P < 0.0001), compared to healthy controls. Addition of protease inhibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks affinity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight underlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.
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| 8. |
- Lönn, Johanna, 1982-, et al.
(författare)
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P. gingivalis-induced aggregation and ros production in whole blood is dependent on gingipains
- 2012
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Ingår i: Cardiovascular Research. - Oxford, United Kingdom : Oxford University Press. - 0008-6363 .- 1755-3245. ; 93, s. S35-S35
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A large body of data accumulated over the past several years suggests that the periodontal pathogen Porphyromonas gingivalis is associated with cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygen species (ROS) production and aggregation. We have previously demonstrated that P. gingivalis induces aggregation and ROS production in whole blood, and that the anti-inflammatory mediator lipoxin A4 (LXA4) inhibits these responses by modulating plateletneutrophil interaction through a down-regulation of the bacterium-induced surface expression of CD11b/CD18 on neutrophils, likely by inhibiting Rac2 and Cdc42 signaling pathways. Furthermore, P. gingivalis, unlike other periodontopathic bacteria, has been shown to trigger platelet aggregation, mainly through the interaction between bacterial gingipains and protease-activating receptors (PARs) on the platelets. Since platelet aggregation precedes thromboembolic events, this is an important pathogenic feature of the bacterium. The aim of this study was to investigate the effect of gingipains on P. gingivalis-induced cell activation in whole blood. Platelet/leukocyte aggregation and ROS production was examined by lumiaggregometry. This study shows that leupeptin, a protease inhibitor of gingipains, inhibits P. gingivalis-induced aggregation and ROS production in whole blood. Supernatants of bacteria suspensions induced no ROS-production, but an aggregatory response that was also inhibited by leupeptin. In conclusion, P. gingivalis-induced aggregation and ROS production in whole blood is mainly dependent on gingipains. However, since bacterial supernatants (containing soluble gingipains) stimulate only aggregation, this suggests that a gingipain/PAR-mediated mechanism in combination with phagocytosis of whole bacterium is a prerequisite for inducing a respiratory burst and an inflammatory response. These findings may contribute to new strategies in the prevention and treatment of periodontitis-induced inflammatory disorders, such as atherosclerosis.
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| 9. |
- Lönn, Johanna, 1982-
(författare)
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The role of peridontitis and hepatocyte growth factor in systemic inflammation
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An essential goal in addressing inflammation is the return of tissue to homeostasis. Persistent infections often cause prolonged response and accumulation of immune cells, inducing imbalance in pro- and anti-inflammatory mediators, tissue destruction, and chronic inflammation. In periodontal disease, bacteria of the dental plaque are the primary aetiologic agents. Coronary artery disease (CAD) and chronic renal failure (CRF) are associated with periodontitis and involve systemic inflammation with atherosclerotic and fibrotic processes. The aims of this thesis were to study the effect of the bacterium Porphyromonas gingivalis and the anti-inflammatory mediator lipoxin A4 (LXA4) on blood cells in vitro, as well as to measure the expression of hepatocyte growth factor (HGF) in patients with periodontitis, CAD, and CRF. We found that LXA4 inhibits P. gingivalis–induced leukocyte platelet aggregation and reactive oxygen species (ROS) production in whole blood, by antagonizing the upregulation of CD11b/CD18 on leukocytes. The serum concentration of HGF was elevated in patients with periodontitis, CAD and CRF, indicating a systemic inflammation. However, the biological activity of HGF was reduced in serum from CRF patients and in saliva and gingival crevicular fluid of patients with periodontitis. This finding correlated with reduced growth of gingival epithelial cells incubated with saliva from patients with periodontitis. Neutrophil proteases reduced the biological activity of HGF in patients with CRF, and HGF expression in patients with periodontitis was associated with higher concentration and numbers of species of periodontal bacteria. In conclusion, these studies suggest that systemic spreading of periodontal bacteria, leukocyte-platelet activation and disturbed HGF-expression are crucial components involved in tissue degradation and progression of chronic inflammation.
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| 10. |
- Nakka, Sravya Sowdamini, 1988-, et al.
(författare)
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Antibodies produced in vitro in the detection of periodontal bacteria by using surface plasmon resonance analysis
- 2015
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Ingår i: Clinical and Experimental Dental Research. - : Wiley-Blackwell. - 2057-4347. ; 1:1, s. 32-44
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Tidskriftsartikel (refereegranskat)abstract
- Porphyromonas gingivalis (P. gingivalis) is a major etiological agent associated with periodontitis. This study aims to develop antibodies to P. gingivalis in vitro for real-time detection of bacteria in clinical samples. Lymphocytes were isolated from whole blood of patient treated for periodontitis and were stimulated with P. gingivalis ATCC 33277. B-cell maturation to long-living antibody secreting-plasma cells was studied using flow cytometry and immunofluorescence staining. The antibodies developed in vitro were immobilized onto a CM-5 sensor chip of a biosensor to detect the presence of P. gingivalis in the gingival crevicular fluid of patients with periodontitis compared to periodontally healthy controls (n = 30). Surface plasmon resonance (SPR) analysis was performed to evaluate specific interactions of bacteria in samples with the immobilized antibodies. The results of SPR analysis were compared to the detection of P. gingivalis in the samples using DNA–DNA checkerboard hybridization technique. A clear and distinct change in lymphocyte morphology upon stimulation with P. gingivalis was observed. Anti-P. gingivalis antibodies secreted by CD38+ plasma cells showed the presence of all the four IgG subclasses. The results of DNA–DNA checkerboard analysis were in agreement with that of SPR analysis for the detection of P. gingivalis in patient samples. Furthermore, incubation with anti-P. gingivalis attenuated the bacterial response in SPR. The in vitro method for antibody production developed during this study could be used for an efficient real-time detection of periodontitis, and the attenuating effects of in vitro antibodies suggest their role in passive immunization to prevent periodontitis and their associated risk factors.
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