| 1. |
- Kutty Selva, Nandakumar, et al.
(författare)
-
A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.
- 2010
-
Ingår i: PLoS ONE. - San Francisco, CA : Public Library of Science (PLoS). - 1932-6203. ; 5:10
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To develop and validate a recombinant vaccine to attenuate inflammation in arthritis by sustained neutralization of the anaphylatoxin C5a. METHODS: We constructed and expressed fusion protein of C5a and maltose binding protein. Efficacy of specific C5a neutralization was tested using the fusion protein as vaccine in three different arthritis mouse models: collagen induced arthritis (CIA), chronic relapsing CIA and collagen antibody induced arthritis (CAIA). Levels of anti-C5a antibodies and anti-collagen type II were measured by ELISA. C5a neutralization assay was done using a rat basophilic leukemia cell-line transfected with the human C5aR. Complement activity was determined using a hemolytic assay and joint morphology was assessed by histology. RESULTS: Vaccination of mice with MBP-C5a led to significant reduction of arthritis incidence and severity but not anti-collagen antibody synthesis. Histology of the MBP-C5a and control (MBP or PBS) vaccinated mice paws confirmed the vaccination effect. Sera from the vaccinated mice developed C5a-specific neutralizing antibodies, however C5 activation and formation of the membrane attack complex by C5b were not significantly altered. CONCLUSIONS: Exploitation of host immune response to generate sustained C5a neutralizing antibodies without significantly compromising C5/C5b activity is a useful strategy for developing an effective vaccine for antibody mediated and C5a dependent inflammatory diseases. Further developing of such a therapeutic vaccine would be more optimal and cost effective to attenuate inflammation without affecting host immunity.
|
|
| 2. |
- Teneberg, Susanne, et al.
(författare)
-
Lactotetraosylceramide, a novel glycosphingolipid receptor for Helicobacter pylori, present in human gastric epithelium
- 2002
-
Ingår i: Journal of Biological Chemistry. - Bethesda : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 277:22, s. 19709-19719
-
Tidskriftsartikel (refereegranskat)abstract
- The binding of Helicobacter pylori to glycosphingolipids was examined by binding of 35S-labeled bacteria to glycosphingolipids on thin-layer chromatograms. In addition to previously reported binding specificities, a selective binding to a non-acid tetraglycosylceramide of human meconium was found. This H. pylori binding glycosphingolipid was isolated and, on the basis of mass spectrometry, proton NMR spectroscopy, and degradation studies, were identified as Galβ3GlcNAcβ3-Galβ4Glcβ1Cer (lactotetraosylceramide). When using non-acid glycosphingolipid preparations from human gastric epithelial cells, an identical binding of H. pylori to the tetraglycosylceramide interval was obtained in one of seven samples. Evidence for the presence of lactotetraosylceramide in the binding-active interval was obtained by proton NMR spectroscopy of intact glycosphingolipids and by gas chromatography-electron ionization mass spectrometry of permethylated tetrasaccharides obtained by ceramide glycanase hydrolysis. The lactotetraosylceramide binding property was detected in 65 of 74 H. pylori isolates (88%) Binding of H. pylori to lactotetraosylceramide on thin-layer chromatograms was inhibited by preincubation with lactotetraose but not with lactose. Removal of the terminal galactose of lactotetraosylceramide by galactosidase hydrolysis abolished the binding as did hydrazinolysis of the acetamido group of the N-acetylglucosamine. Therefore, Galβ3GlcNAc is an essential part of the binding epitope.
|
|
| 3. |
- Bersellini Farinotti, Alex, et al.
(författare)
-
Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons
- 2019
-
Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:8, s. 1904-1924
-
Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.
|
|
| 4. |
- Shen, Weixing, et al.
(författare)
-
Protective effects of Wang-Bi tablet on bone destruction in collagen-induced arthritis by regulating osteoclast-osteoblast functions.
- 2019
-
Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 238
-
Tidskriftsartikel (refereegranskat)abstract
- ETHNOPHARMACOLOGICAL RELEVANCE: Wang-bi tablet (WB) consists of 17 traditional Chinese medicines and has been used for treating rheumatoid arthritis (RA) in China for many years, however, its pharmacologic mechanism is not clear.AIM OF STUDY: The aim of this study was to investigate the therapeutic effect of WB on collagen-induced mouse arthritis and explored the underlying mechanism.MATERIALS AND METHODS: DBA/1 mice were used to establish a type II collagen-induced arthritis (CIA) model. From the day of arthritis onset, mice were treated daily by gavage with either total glucosides of paeony (TGP, 0.37 g/kg/d) or WB at a lower (1.11 g/kg/d, WBL) or higher dose of (3.33 g/kg/d, WBH) for 8 weeks. The severity of arthritis, levels of cytokines and the activation of signaling pathways were determined.RESULTS: Our results revealed that WB treatment effectively alleviated inflammatory symptoms and prevented bone erosions and joint destructions. It obviously decreased the serum concentration of pro-inflammatory cytokines TNF-α, IL-6 and IL-17α, while increased the concentration of anti-inflammatory cytokine IL-10. Interestingly, the proportion of splenic Treg cells were increased significantly. In vitro experiments showed that WB inhibited the differentiation of osteoclasts. Consistently, the mRNA levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CtsK), and the activation of NF-κB and JAK-STAT3 signaling pathways in the paws of CIA mice were inhibited by WB treatment. On the other hand, up-regulation of osteogenic genes Runx2, Osterix mRNA, and activation of Wnt/β-catenin signaling pathway along with a decreased receptor activator of nuclear factor κB ligand (RANKL) expression were found in WB treated mice.CONCLUSION: Our results suggest that the therapeutic effect of Wang-bi tablet could be attributed to its inhibitory activity on NF-κB and STAT3 signaling pathway-mediated osteoclast differentiation, and its enhancement on Wnt/β-catenin signaling pathway-mediated osteoblast functions.
|
|
| 5. |
- Lahore, G. F., et al.
(författare)
-
Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases
- 2020
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:40, s. 24986-24997
-
Tidskriftsartikel (refereegranskat)abstract
- It has proven difficult to identify the underlying genes in complex autoimmune diseases. Here, we use forward genetics to identify polymorphisms in the vitamin D receptor gene (Vdr) promoter, controlling Vdr expression and T cell activation. We isolated these polymorphisms in a congenic mouse line, allowing us to study the immunomodulatory properties of VDR in a physiological context. Congenic mice overexpressed VDR selectively in T cells, and thus did not suffer from calcemic effects. VDR overexpression resulted in an enhanced antigen-specific T cell response and more severe autoimmune phenotypes. In contrast, vitamin D3-deficiency inhibited T cell responses and protected mice from developing autoimmune arthritis. Our observations are likely translatable to humans, as Vdr is overexpressed in rheumatic joints. Genetic control of VDR availability codetermines the proinflammatory behavior of T cells, suggesting that increased presence of VDR at the site of inflammation might limit the antiinflammatory properties of its ligand.
|
|
| 6. |
- Nandakumar, Kutty Selva, 1965-, et al.
(författare)
-
A genetic contamination in MHC-congenic mouse strains reveals a locus on chromosome 10 that determines autoimmunity and arthritis susceptibility
- 2005
-
Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 35:4, s. 1275-1282
-
Tidskriftsartikel (refereegranskat)abstract
- Among the arthritis-susceptible MHC (H-2)-congenic mouse strains, B10.RIII mice are highly susceptible to collagen-induced arthritis. Surprisingly, the B10.RIII strain was also more susceptible to the T cell independent model CAIA (collagen-antibody-induced arthritis). Through genome-wide genotyping, we found that the B10.RIII and B10.Q strains differed not only in chromosome 17 (MHC) but also in a region on chromosome 10, which contained a fragment from the MHC donor RIIIS/J. We isolated the chromosome 10 as well as the chromosome 17 segments on the B10.RIII and B10.Q backgrounds. Congenic mice containing the RIIIS/J-derived chromosome 10 segment showed significantly higher susceptibility and severity of arthritis with an enhanced autoimmune response to type II collagen. Furthermore, this chromosomal segment significantly promoted CAIA. Similarly, the RIIIS/J segment in chromosome 17 also promoted CAIA independently of other gene segments. These data show that other gene regions, apart from MHC class II, may explain effects both at the priming and effector level of arthritis observed in widely used MHC congenic strains. These new congenic fragments, on both chromosome 10 and 17, provide new mouse strains suitable for studies aiming at positional cloning of new genes associated with arthritis.
|
|
| 7. |
- Urrutia-Cordero, Pablo, et al.
(författare)
-
Effects of harmful cyanobacteria on the freshwater pathogenic free-living amoeba Acanthamoeba castellanii
- 2013
-
Ingår i: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 130, s. 9-17
-
Tidskriftsartikel (refereegranskat)abstract
- Grazing is a major regulating factor in cyanobacterial population dynamics and, subsequently, considerable effort has been spent on investigating the effects of cyanotoxins on major metazoan grazers. However, protozoan grazers such as free-living amoebae can also feed efficiently on cyanobacteria, while simultaneously posing a major threat for public health as parasites of humans and potential reservoirs of opportunistic pathogens. In this study, we conducted several experiments in which the freshwater amoeba Acanthamoeba castellanii was exposed to pure microcystin-LR (MC-LR) and six cyanobacterial strains, three MC-producing strains (MC-LR, MC-RR, MC-YR, MC-WR, [Dha7] MC-RR) and three strains containing other oligopeptides such as anabaenopeptins and cyanopeptolins. Although the exposure to high concentrations of pure MC-LR yielded no effects on amoeba, all MC-producing strains inflicted high mortality rates on amoeba populations, suggesting that toxic effects must be mediated through the ingestion of toxic cells. Interestingly, an anabaenopeptin-producing strain caused the greatest inhibition of amoeba growth, indicating that toxic bioactive compounds other than MCs are of great importance for amoebae grazers. Confocal scanning microscopy revealed different alterations in amoeba cytoskeleton integrity and as such, the observed declines in amoeba densities could have indeed been caused via a cascade of cellular events primarily triggered by oligopeptides with protein-phosphatase inhibition capabilities such as MCs or anabaenopeptins. Moreover, inducible-defense mechanisms such as the egestion of toxic, MC-producing cyanobacterial cells and the increase of resting stages (encystation) in amoebae co-cultivated with all cyanobacterial strains were observed in our experiments. Consequently, cyanobacterial strains showed different susceptibilities to amoeba grazing which were possibly influenced by the potentiality of their toxic secondary metabolites. Hence, this study shows the importance of cyanobacterial toxicity against amoeba grazing and, that cyanobacteria may contain a wide range of chemical compounds capable of negatively affect free-living, herbivorous amoebae. Moreover, this is of high importance for understanding the interactions and population dynamics of such organisms in aquatic ecosystems. (c) 2012 Elsevier B.V. All rights reserved.
|
|
| 8. |
- Adamsson, Viola, et al.
(författare)
-
Effects of a Nordic diet on cardiovascular and metabolic risk factors in hypercholesterolemic subjects: a randomized controlled study
- 2009
-
Konferensbidrag (refereegranskat)abstract
- Background: Apart from lipid-lowering drugs, dietary changes can also reduce plasma LDL-C concentrations. No studies have been conducted to investigate the clinical effects of a diet with traditional foods originating from the Nordic countries. Method: In a randomised, controlled parallel-group intervention study 88 mildly hypercholesterolemic men and women were randomized to either an ad libitum Nordic diet (ND) or a control diet (CD) for 6 weeks. All meals and foods were provided to the participants in the ND group. Primary outcome measure was LDL-cholesterol, and secondary outcomes were blood pressure, plasma insulin and glucose concentrations. The ND was a high-fibre diet rich in plant foods (fruit, berries, vegetables, root vegetables, whole grain cereals and legumes), vegetable fats (rapeseed oil and nuts) and fatty fish, low-fat milk products, but low in salt, added sugars, saturated fats and red meats. Result: 86 subjects completed the study. Distribution of carbohydrates, fat and protein (E%) in ND was 54, 27, 19, respectively. ND lowered plasma total cholesterol 0.98±0.75 mmol/l (-16%), LDL-C by 0.83±0.67 mmol/l (-21%), HDL-C 0.08±0.23 mmol/l (-5%), including reduced LDL/HDL ratio by -0.42±0.57 (-14%) (all p<0.01 versus controls). Insulin concentrations decreased by 0.51± 2.25 (-9%, p=0.01) and systolic blood pressure by 7±13 mmHg (-5%, P<0.01) compared to controls. Despite diets were eaten ad libitum, body weight decreased by 3.0 kg in the ND (P<0.001). No significant differences were found for diastolic blood pressure, triglycerides or plasma glucose. Conclusion: A Nordic diet improves blood lipid profile, and insulin sensitivity as well as lowering blood pressure to a clinically significant extent in hypercholesterolemic subjects.
|
|
| 9. |
- Antonelo, Eric A., et al.
(författare)
-
Modular Neural Network and Classical Reinforcement Learning for Autonomous Robot Navigation : Inhibiting Undesirable Behaviors
- 2006
-
Ingår i: International Joint Conference on Neural Networks, 2006. IJCNN '06. - Piscataway, N.J. : IEEE Press. - 0780394909 ; , s. 498-505
-
Konferensbidrag (refereegranskat)abstract
- Classical reinforcement learning mechanisms and a modular neural network are unified for conceiving an intelligent autonomous system for mobile robot navigation. The conception aims at inhibiting two common navigation deficiencies: generation of unsuitable cyclic trajectories and ineffectiveness in risky configurations. Distinct design apparatuses are considered for tackling these navigation difficulties, for instance: 1) neuron parameter for memorizing neuron activities (also functioning as a learning factor), 2) reinforcement learning mechanisms for adjusting neuron parameters (not only synapse weights), and 3) a inner-triggered reinforcement. Simulation results show that the proposed system circumvents difficulties caused by specific environment configurations, improving the relation between collisions and captures.
|
|
| 10. |
- Arakelyan, Arsen, et al.
(författare)
-
Functional Genetic Polymorphisms of Monocyte Chemoattractant Protein 1 and C-C Chemokine Receptor Type 2 in Ischemic Stroke
- 2014
-
Ingår i: Journal of Interferon and Cytokine Research. - New Rochelle, NY : Mary Ann Liebert. - 1079-9907 .- 1557-7465. ; 34:2, s. 100-105
-
Tidskriftsartikel (refereegranskat)abstract
- Recent findings indicated that monocyte chemoattractant protein 1 (MCP1) and its C-C chemokine receptor type 2 (CCR2) play a key role in ischemic stroke (IS) progression. This study was aimed at evaluating the potential association of the MCP1 gene (MCP1) rs1024611 (-2518 A>G) and CCR2 gene (CCR2) rs1799864 (V64I; 190 G>A) functional single nucleotide polymorphisms (SNPs) with IS in the Armenian population. For the purpose of this study, genomic DNA samples of 100 patients with the first-episode IS and 115 healthy subjects (controls) were genotyped for the selected SNPs using a polymerase chain reaction with sequence-specific primers. The results obtained demonstrated that while the CCR2 rs1799864 SNP genotypes were equally distributed among patients and controls, the frequency and carriage rate of the of the MCP1 rs1024611*G minor allele were higher in patients. While a potential association between IS and CCR2 rs1799864 SNP was evaluated for the first time, the latest finding was in agreement with the earlier data reported for some other populations. In summary, this study revealed no association of CCR2 rs1799864 SNP with IS, and a positive association between G minor allele of MCP1 rs1024611 SNP and IS in the Armenian population. Based on the present and earlier reported data, we concluded that the minor G allele of the MCP1 rs1024611 SNP might be considered a risk factor for IS.
|
|
