| 1. |
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| 2. |
- Tarkowski, E, et al.
(author)
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Cerebral pattern of pro- and anti-inflammatory cytokines in dementias
- 2003
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In: Brain Research Bulletin. - 0361-9230. ; 61:3, s. 255-260
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Journal article (peer-reviewed)abstract
- The knowledge regarding putative inflammatory component(s) participating in Alzheimer's disease (AD) and vascular dementia (VAD) is scarce. Recently, we have demonstrated the presence of certain inflammatory cytokines in the cerebrospinal fluid (CSF) of demented patients. Although the initial event(s) triggering the neurodegenerative processes in AD versus VAD may be different and lead to different neuropathological changes, it may initiate a similar cascade of cytokine production in response to neuronal injury. The cytokines released in the central nervous system (CNS) may, in turn, act in a similar manner in both diseases, amplifying some pathological changes such as amyloidogenesis and white matter lesions or on the contrary acting as neuroprotective molecules. This review will focus on the intracerebral production of the pro- and anti-inflammatory cytokines interleukin IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-6 and TNF-alpha in dementia, and their relation to gene polymorphism, to cerebral neuronal damage, apoptosis, and to clinical variables of dementia. Our results, which show for the first time strikingly increased CSF levels of TNF-alpha but not of TNF-beta, IL-1beta or IL-6 in AD and VAD, may form a conceptual framework for further studies of neuroprotective mechanisms in dementias. (C) 2003 Elsevier Science Inc. All rights reserved.
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| 3. |
- Tarkowski, E, et al.
(author)
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TNF gene polymorphism and its relation to intracerebral production of TNFalpha and TNFbeta in AD
- 2000
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In: Neurology. - 1526-632X. ; 54:11, s. 2077-2081
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To analyze the extent of tumor necrosis factor-alpha (TNFalpha) and TNFbeta gene polymorphism in patients with AD and to relate it to intrathecal levels of these cytokines. METHODS: Analyses of TNFalpha and TNFbeta gene polymorphism were performed using PCR in 52 patients with AD and in 25 control subjects, and the levels of corresponding cytokines were analyzed using ELISA. RESULTS: Patients with AD displayed significantly higher intrathecal levels of TNFalpha, but not TNFbeta, compared with the control subjects. The levels of these cytokines did not differ significantly in patients displaying different alleles of the TNF gene. CONCLUSIONS: Results indicate that increased intrathecal production of TNFalpha in AD is preferentially controlled by environmental stimuli rather than genetic makeup.
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| 4. |
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| 5. |
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| 6. |
- Bergquist, Jonas, et al.
(author)
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Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop.
- 1994
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In: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 91:26, s. 12912-6
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Journal article (peer-reviewed)abstract
- Evidence has been obtained that catecholamines and their metabolites are present in single lymphocytes and extracts of T- and B-cell clones by use of capillary electrophoresis with electrochemical detection. Pharmacological inhibition of tyrosine hydroxylase reduces observed catecholamine levels, suggesting catecholamine synthesis by lymphocytes. Intracellular dopamine levels are shown to be increased by extra-cellular dopamine, suggesting a cellular-uptake mechanism. Furthermore, incubation with either dopamine or L-dihydroxyphenylalanine, a precursor of dopamine, results in a dose-dependent inhibition of lymphocyte proliferation and differentiation. Together, these results suggest the presence of an autocrine loop whereby lymphocytes down-regulate their own activity.
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| 7. |
- Bergquist, Jonas, et al.
(author)
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Measurements of catecholamine-mediated apoptosis of immunocompetent cells by capillary electrophoresis.
- 1997
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In: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 18:10, s. 1760-6
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Journal article (peer-reviewed)abstract
- Single cell analysis with capillary electrophoresis, a technique capable of detecting zeptomole quantities (10(-21) mole) of neurochemical species, has been used to demonstrate that lymphocytes are capable of active synthesis of dopamine and norepinephrine. Exposure of lymphocytes to catecholamines at concentrations as low as 10 nM leads to decreased proliferation and differentiation, e.g. interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and immunoglobulin (Ig). In addition, both inhibition of dopamine uptake with nomifensine and inhibition of packing of catecholamines into vesicles with tetrabenazine, results in significantly lower levels of dopamine and norepinephrine (p < 0.01 and p < 0.05, respectively). The catecholamine-dependent inhibition of T- and B-lymphocyte activity is mediated via an induction of a Bcl-2/Bax and Fas/FasL involved apoptosis. These findings indicate a novel mechanism for regulation of lymphocyte activity in the central nervous system, whereby elevated regional levels of catecholamines might lead to the immunoprivilege of the brain.
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| 8. |
- Hogevik, Harriet, et al.
(author)
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Virulence factors of Staphylococcus aureus strains causing infective endocarditis--a comparison with strains from skin infections.
- 1998
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In: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0903-4641 .- 0903-465X .- 1600-5503 .- 1600-0463. ; 106:9, s. 901-8
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Journal article (peer-reviewed)abstract
- The objective was to study potential bacterial virulence factors in S. aureus endocarditis. S. aureus strains isolated from patients with well-classified episodes of infective endocarditis (IE) (n=26) were compared with control S. aureus strains from consecutive patients with skin infections (n=30). The potential virulence factors studied were Staphylococcal enterotoxin A-D (SEA, SEB, SEC, SED) and toxic shock syndrome toxin-1 (TSST-1) production and binding capacity to the extracellular matrix proteins: fibronectin, collagen type I, collagen type II and bone sialoprotein (BSP). None of the potential virulence factors studied was more prevalent among the IE strains. BSP binding was more often found in the control group with skin infections. Endocarditis patients with previous damage of the heart valves were more often infected by strains not producing any enterotoxin. No correlation was found between the potential bacterial virulence factors studied and IE. Concerning the toxins known to act as superantigens (SEA-E and TSST-1), the tendencies in this and other studies indicate that a larger study group might identify them as pathogenic factors in a subgroup of staphylococcal endocarditis.
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| 9. |
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| 10. |
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| 11. |
- Mattsson, Niklas, 1979, et al.
(author)
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Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.
- 2009
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 15:4, s. 448-54
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cell and animal experiments have shown that beta-site APP-cleaving enzyme 1 (BACE1) may be involved in myelination. OBJECTIVE: Here, we assess the association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis (MS). METHODS: BACE1 activity and levels of secreted amyloid precursor protein (APP) and amyloid-beta (Abeta) isoforms were analyzed in CSF from 100 patients with MS and 114 neurologically healthy controls. Patients with systemic lupus erythematosus (SLE), 26 with and 41 without cerebral engagement, were also included to enable comparisons with regards to another autoimmune disease. A subset of patients with MS and controls underwent a second lumbar puncture after 10 years. RESULTS: MS patients had lower CSF BACE1 activity than controls (P = 0.03) and patients with cerebral SLE (P < 0.001). Patients with cerebral SLE had higher BACE1 activity than any other group (P < 0.05 for all comparisons). BACE1 activity correlated with the different amyloid markers in all study groups. BACE1 activity decreased over 10 years in the MS group (P = 0.039) and correlated weakly with clinical disease severity scores in an inverse manner. CONCLUSIONS: These results suggest an involvement of BACE1 in the MS disease process.
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| 12. |
- Mölne, L, et al.
(author)
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Role of gamma/delta T cell receptor-expressing lymphocytes in cutaneous infection caused by Staphylococcus aureus.
- 2003
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In: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 132:2, s. 209-215
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Journal article (peer-reviewed)abstract
- The high number of /-expressing T cells found in the epithelial lining layer suggests that they form a first line of defence against invading pathogens. To evaluate the role of / T cell-receptor (TCR)-expressing cells in cutaneous infection caused by Staphylococcus aureus, mice lacking /-expressing T cells (TCR/) were inoculated intradermally with S. aureus, and compared with S. aureus-infected congeneic TCR+/ control mice. The number of bacteria recovered from the skin of TCR/ mice was significantly higher (P = 0·0071) at early time-points after inoculation compared to the number of bacteria isolated from infected TCR+/ congeneic controls. Nevertheless, inflammatory responses measured as serum IL-6 levels, were significantly lower in TCR/ mice than in the control group. A possible explanation for this discrepancy was the observation of significantly decreased overall numbers of infiltrating cutaneous T lymphocytes, which are important producers of IL-6. These results support the notion that the /-expressing T cells that reside at the epithelial lining layer of the skin is of importance for early containment of the bacteria, thereby limiting their replication and spread.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Calander, Ann-Marie, 1957, et al.
(author)
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Impact of staphylococcal protease expression on the outcome of infectious arthritis
- 2004
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In: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 6:2, s. 202-6
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Journal article (peer-reviewed)abstract
- The exoproteases of Staphylococcus aureus have been proposed as virulence factors during S. aureus infections. To investigate this, we used the wild-type S. aureus strain 8325-4 and its mutants devoid of aureolysin, serine protease, and cysteine protease, respectively, in a well-established model of septic arthritis in mice. The inactivation of the exoprotease genes did not affect the frequency or the severity of joint disease. We conclude that in the model of haematogenously spread staphylococcal arthritis, the bacterial proteases studied do not act as virulence factors.
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| 18. |
- Carlsten, Hans, 1954, et al.
(author)
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The impact of a new immunomodulator oxo-quinoline-3-carboxamide on the progression of experimental lupus
- 2004
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In: Int Immunopharmacol. - : Elsevier BV. - 1567-5769. ; 4:12, s. 1515-23
-
Journal article (peer-reviewed)abstract
- Autoimmune, lupus-prone MRL lpr/lpr mice were treated orally with oxo-quinoline-3-carboxamide (ABR-25757), a newly developed immunomodulator. Treatment was initiated in one set of experiment at the age of 10 weeks, before the onset of clinically apparent disease, and in another set at 15 weeks, after the development of established lupus disease. Beneficial therapeutic effects were obtained even when ABR-25757 was administered at the lowest dose tested (7.5 microg/mouse/week) to 15 weeks old mice with established lupus disease. The effects of ABR-25757 on longevity, as well as on development of glomerulonephritis were pronounced and comparable with those of LS-2616, a potent immunomodulator. Administration of ABR-25757 did not significantly alter T cell responses in vivo nor in vitro. In addition, it only marginally suppressed B cell responses measured as frequencies of immunoglobulin secreting cells. By the same token this compound did not affect overall leukocyte content in primary (bone marrow) or secondary (spleen) lymphoid tissues. In contrast, treatment with ABR-25757 up regulated expression of pro-inflammatory transcription factors NF-kappaB and AP-1. These results suggest (a) a potential therapeutic role of ABR-25757 in the treatment of experimental lupus and (b) that the effect of the treatment is mediated by immunodeviation rather than by immunosuppression.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Gjertsson, Inger, 1962, et al.
(author)
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Impact of transcription factors AP-1 and NF-kappaB on the outcome of experimental Staphylococcus aureus arthritis and sepsis.
- 2001
-
In: Microbes and infection. - 1286-4579. ; 3:7, s. 527-34
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Journal article (peer-reviewed)abstract
- Staphylococcus aureus infection is, despite adequate antibiotic treatment, a disease characterized by high mortality. The bacterium triggers an exaggerated immune response in the host, which on the one hand acts as an efficient defense, but on the other hand gives rise to tissue damage. In this study we have modulated the hosts response to S. aureus by inhibition of nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1)-triggered release of pro-inflammatory cytokines and tissue-destructive proteins, respectively. Mice were administered with antisense oligonucleotides (ODN) to the p65 subunit of NF-kappaB and/or a double-stranded oligonucleotide (mCoAP-1) with homology to the murine AP-1 binding site of collagenase IV gene (metalloproteinase-9; MMP-9), solely or in combination with antibiotics. In mice systemically treated with antisense ODN to NF-kappaB p65 alone, the bacterial burden in the kidneys was significantly increased (P = 0.04) The same tendency was seen when mCoAP-1 was administered either alone or in combination with antibiotics. We also found significantly (P = 0.04) elevated levels of IL-6 in p65 antisense treated mice. Surprisingly, this p65 antisense therapy approach, which has turned out to be highly efficient in amelioration of aseptic arthritis and colitis, failed to change the clinical course of either septic arthritis or sepsis. We suggest that interaction with transcription factors leads to increased bacterial burden in vivo, abrogating the potential benefits of the anti-inflammatory properties exerted by these compounds.
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| 23. |
- Guo, J P, et al.
(author)
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The rat antigen-presenting lectin-like receptor complex influences innate immunity and development of infectious diseases.
- 2009
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In: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 10:3, s. 227-36
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Journal article (peer-reviewed)abstract
- Genetic variation in the antigen-presenting lectin-like receptor gene complex (APLEC) associates with autoimmunity and arthritis in rats and humans. We hypothesized that the encoded C-type lectin-like receptors might influence innate immunity and responses to infectious agents. To test this hypothesis, we compared in vivo and in vitro phenotypes in DA rats and APLEC-congenic rats. Survival rates following infection with Staphylococcus aureus and Herpes simplex virus differed significantly between the two strains. Likewise, differential delayed type hypersensitivity (DTH), an immunological reaction involving T lymphocytes and macrophages, was observed in response to provocation with the chemical oxazolone. Unstimulated bone marrow-derived macrophages from the two strains appeared to already have polarized activation states with different mRNA levels of CD163 and Dectin-1 receptors. Following stimulation with a panel of microbial agents, differences in induced mRNA and protein levels were shown for interleukin (IL)-6 and IL-10 following stimulation with lipopolysaccharide, mannan and beta-glucan. Expression levels of APLEC gene mRNAs also differed, and both strains had a notably dichotomous expression of the genes, with general downregulation of all four Dcir genes and upregulation of Mincle and Mcl. We suggest that human APLEC genes may similarly regulate infectious diseases, DTH and general macrophage activation status.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Josefsson, E, et al.
(author)
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Catecholamines are synthesized by mouse lymphocytes and regulate function of these cells by induction of apoptosis.
- 1996
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In: Immunology. - 0019-2805 .- 1365-2567. ; 88:1, s. 140-6
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Journal article (peer-reviewed)abstract
- The immune and the nervous systems are anatomically closely related and interact with each other by molecules common to both systems, such as cytokines and neurotransmitters. The purpose of this study was to investigate the participation of catecholamines in the neuroimmunological network. The ability of immune cells to produce catecholamines was examined by a highly sensitive capillary electrophoresis assay, which permits detection of easily oxidized catecholamines in the zeptomole (10(-21)) range. In addition, the effects of catecholamines on in vitro proliferation, differentiation and apoptosis of lymphocytes were assessed. Mouse spleen cells and macrophages contained on average 7 x 10(-17) and 2 x 10(-17) mole dopamine per cell, respectively. In the former cell population also norepinephrine was found. Several mouse B- and T-cell hybridomas were also shown to contain endogenously produced dopamine in levels ranging from 7 x 10(-20) to 2 x 10(-18) mole dopamine per cell. In addition, one of the T-cell hybridomas proved to synthesize norepinephrine. The dopamine production of lymphocytes was blocked by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine, whereas incubation with the precursor L-DOPA increased the dopamine content. Incubation with L-DOPA, dopamine and norepinephrine dose-dependently suppressed mitogen induced proliferation and differentiation of mouse lymphocytes. Even short-time pretreatment of lymphocytes with L-DOPA and dopamine strongly suppressed lymphocyte proliferation and cytokine production. Incubation of lymphoid cells with L-DOPA, dopamine and norepinephrine dose-dependently induced apoptosis which, at least partly, explains the suppressive effects of catecholamines on lymphocyte function. Our results demonstrate that catecholamines: (i) are actively produced by lymphocytes and (ii) have the capacity to act as auto- and/or paracrine regulators of lymphocyte activity through induction of apoptosis.
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| 28. |
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| 29. |
- Kenny, John G, et al.
(author)
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The Staphylococcus aureus response to unsaturated long chain free fatty acids: survival mechanisms and virulence implications.
- 2009
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In: PLoS ONE. ; 4:2
-
Journal article (peer-reviewed)abstract
- Staphylococcus aureus is an important human commensal and opportunistic pathogen responsible for a wide range of infections. Long chain unsaturated free fatty acids represent a barrier to colonisation and infection by S. aureus and act as an antimicrobial component of the innate immune system where they are found on epithelial surfaces and in abscesses. Despite many contradictory reports, the precise anti-staphylococcal mode of action of free fatty acids remains undetermined. In this study, transcriptional (microarrays and qRT-PCR) and translational (proteomics) analyses were applied to ascertain the response of S. aureus to a range of free fatty acids. An increase in expression of the sigma(B) and CtsR stress response regulons was observed. This included increased expression of genes associated with staphyloxanthin synthesis, which has been linked to membrane stabilisation. Similarly, up-regulation of genes involved in capsule formation was recorded as were significant changes in the expression of genes associated with peptidoglycan synthesis and regulation. Overall, alterations were recorded predominantly in pathways involved in cellular energetics. In addition, sensitivity to linoleic acid of a range of defined (sigB, arcA, sasF, sarA, agr, crtM) and transposon-derived mutants (vraE, SAR2632) was determined. Taken together, these data indicate a common mode of action for long chain unsaturated fatty acids that involves disruption of the cell membrane, leading to interference with energy production within the bacterial cell. Contrary to data reported for other strains, the clinically important EMRSA-16 strain MRSA252 used in this study showed an increase in expression of the important virulence regulator RNAIII following all of the treatment conditions tested. An adaptive response by S. aureus of reducing cell surface hydrophobicity was also observed. Two fatty acid sensitive mutants created during this study were also shown to diplay altered pathogenesis as assessed by a murine arthritis model. Differences in the prevalence and clinical importance of S. aureus strains might partly be explained by their responses to antimicrobial fatty acids.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Padyukov, L., et al.
(author)
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Polymorphism in promoter region of IL10 gene is associated with rheumatoid arthritis in women
- 2004
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In: J Rheumatol. - 0315-162X. ; 31:3, s. 422-5
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Rheumatoid arthritis (RA) is a genetically complex disease with many possible phenotypes. We investigated IL10 and TNFA gene polymorphisms in a group of Swedish women and men with RA compared with healthy individuals to estimate combinations of alleles specific for the disease. METHODS: We analyzed 264 patients with RA and 286 healthy controls for biallelic single-nucleotide polymorphisms in the -308 position of the TNFA and in the -1087 position of the IL10 gene by polymerase chain reaction with restriction endonuclease mapping. RESULTS: The frequencies of the -308 TNFA genotypes were not different in women and men with RA in comparison to the controls. In contrast, frequencies of the GG, AG, and AA -1087 IL10 genotypes were significantly different in women in the investigated groups: 26%, 58%, and 15% for RA patients and 24%, 54%, and 28% for the controls (chi-square = 8.18, p < 0.02). We confirmed this finding in a separate dataset of female patients and controls. The frequencies of the IL10 genotypes in men were similar in the patients and controls. We found no differences in the distribution of the TNFA or IL10 genotypes in relation to rheumatoid factor in the patients. CONCLUSION: On the basis of IL10 polymorphism, female patients with RA seem to represent a separate disease subgroup.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Tarkowski, A, et al.
(author)
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Model systems: modeling human staphylococcal arthritis and sepsis in the mouse.
- 2001
-
In: Trends in microbiology. - 0966-842X. ; 9:7, s. 321-6
-
Research review (peer-reviewed)abstract
- The staphylococci have been recognized as serious pathogens for over a century and are the etiological agent of a variety of diseases ranging from mild cutaneous infections to often fatal forms of septic arthritis, endocarditis, toxic shock syndrome and sepsis. Despite intensive efforts to halt their spread, they remain the most common cause of community- and nosocomially acquired bacteremia. Murine models of Staphylocococus aureus-mediated arthritis and sepsis exist and are being used to gain a better understanding of the host-bacterium relationship as well to develop better methods of prevention and treatment.
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| 40. |
- Tarkowski, A., et al.
(author)
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Use of anti-thymocyte globulin in the management of refractory systemic autoimmune diseases
- 1993
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In: Scandinavian Journal of Rheumatology. - 0300-9742 .- 1502-7732. ; 22:6, s. 261-6
-
Journal article (peer-reviewed)abstract
- The purpose of our pilot study was to evaluate the short-and long-term efficacy of T-lymphocyte depletion in the management of patients with refractory, systemic autoimmune diseases. Nine patients with severe, therapy-resistant autoimmune diseases were subjected to T-cell depletion procedure using polyclonal anti-T-cell antibodies combined with peroral administration of azathioprine and/or cyclosporine. The proband group consisted of 4 patients with systemic lupus erythematosus, 3 with progressive systemic sclerosis, and 2 with rheumatoid arthritis. Administration of polyclonal anti-T-cell antibodies was performed at a single occasion via a central venous catheter during 9-10 days. Immunological analyses of T-cell phenotypes and function and assessment of organ function (kidneys, lungs, bone-marrow) has been performed prospectively in all the patients studied. This treatment resulted in prompt and long-lasting (mean follow-up time: 25.6 months) improvement of autoimmune hemolytic anemia, glomerulonephritis, lung fibrosis, skin and joint involvements in the majority of cases. Adverse effects of this treatment included two episodes of infection (E. coli and Cytomegalovirus) and three cases of serum sickness, and were all easily managed. We suggest that this treatment modality adopted from transplant rejection therapy could be employed in cases of severe autoimmune diseases unresponsive to regular immunosuppressive treatment.
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| 41. |
- Tarkowski, E, et al.
(author)
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Decreased levels of intrathecal interleukin 1 receptor antagonist in Alzheimer's disease
- 2001
-
In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:5, s. 314-317
-
Journal article (peer-reviewed)abstract
- A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of brain damage in dementia. In previous studies, we have demonstrated intrathecal production of the proinflammatory cytokine tumor necrosis factor (TNF)alpha in patients with Alzheimer's disease (AD). The aim of the present study was to investigate the downstream products of TNF-alpha expression including interleukin (IL)1beta and its naturally occurring antagonist IL-1 receptor agonist (ra) in patients with AD. The cytokine levels were related to neuronal damage, as measured by intrathecal tau and beta-amyloid concentration and certain clinical features of the disease. Fifty-two patients with AD and 25 healthy controls were analyzed with respect to cerebrospinal fluid (CSF) levels of IL-1beta and IL-1ra. CSF IL-1beta was neither detectable in CSF of AD nor in control CSF. In contrast, a significantly lower (p < 0.01) number of patients (24 of 49) than of controls (20 of 24) showed detectable levels of IL-1ra in the CSF. The intrathecal levels of IL-1ra were significantly lower in patients with AD than in the controls. Our study demonstrates a decreased production of the anti-inflammatory compound IL-1ra, suggesting a propensity towards inflammation in patients with AD.
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| 42. |
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| 43. |
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| 44. |
- Verdrengh, M, et al.
(author)
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Genistein as an anti-inflammatory agent
- 2003
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In: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 52:8, s. 341-346
-
Journal article (peer-reviewed)abstract
- Objective and design: The aim of this study was to investigate the impact of the isoflavone genistein on in vivo cell-mediated responses. In addition, we wanted to study the influence of genistein on collagen induced arthritis (CIA) in mice. Methods: Delayed type hypersensitivity reaction (DTH) to oxazolone and the inflammatory response to olive oil were measured in mice treated with genistein. In addition, the impact of genistein treatment on disease progression and outcome of collagen induced arthritis (CIA) was examined. Results: The DTH reaction to oxazolone and the granulocyte-mediated response were significantly suppressed in genistein-treated as compared to control mice. Also, genistein treatment led to decreased levels of oxazolone-specific antibodies. Histologically, mice exposed to genistein and immunized with collagen II displayed somewhat lower degree of inflammation and joint destruction. In addition, serum levels of autoantibodies to collagen II were significantly lower following genistein-treatment in immunized mice. Conclusion: We conclude that genistein exerts evident anti-inflammatory properties affecting granulocytes, monocytes, and lymphocytes.
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| 45. |
- Verdrengh, M, et al.
(author)
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Integrin-associated protein (IAP)-deficient mice are less susceptible to developing Staphylococcus aureus induced arthritis
- 1999
-
In: Microbes and infection. - 1286-4579 .- 1769-714X. ; 1:10, s. 745-751
-
Journal article (peer-reviewed)abstract
- The integrin-associated protein (IAP) has been shown to function in a signaling complex with β3 integrins, influencing the migration of phagocytic cells into inflamed tissues. We have previously shown that gene-targeted mice deficient for IAP succumbed to peritonitis when inoculated with Gram-negative bacteria. The aim of this study was to assess the role of IAP in our recently established model of haematogenously induced Staphylococcus aureus septicaemia and arthritis. In this model, neutrophils play a crucial role in the early phase of the infection. Mice lacking IAP and congenic controls were intravenously inoculated with S. aureus LS-1. The IAP-/- mice were resistant to developing clinical signs of arthritis compared with their IAP-expressing littermates. The clinical findings were corroborated by histopathological evaluation indicating that the IAP-/- mice had less cartilage and bone destruction in the joints. We believe that a delayed migration of leukocytes into the joints of mice lacking IAP expression leads to decreased susceptibility to develop S. aureus-induced arthritis.
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| 46. |
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| 47. |
- Verdrengh, M, et al.
(author)
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Total abrogation of collagen II-induced arthritis and the B cell response to type II collagen using suboptimal doses of a topoisomerase II antagonist.
- 2002
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 61:9, s. 829-831
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Collagen-induced arthritis (CIA) is the most commonly used model of rheumatoid arthritis (RA). In both CIA and RA there is an increase in the cellular content of the synovium, this being dominated by macrophages. OBJECTIVE: To assess the impact of etoposide, a topoisomerase II antagonist known to induce monocyte apoptosis, on the development of CIA. METHODS: Mice were primed and booster immunised against collagen II (CII). One group of mice was treated with etoposide two days before CII immunisation and then on four consecutive days weekly until the end of the experiment. The second group of mice was injected with etoposide on four consecutive days a week starting 40 days after CII priming. The third group of mice were controls receiving phosphate buffered saline (PBS). The mice were examined for development of arthritis, numbers of circulating leucocytes, serum CII antibody, and cytokine concentrations. RESULTS: None of the mice given etoposide before CII immunisation developed arthritis. Serum concentrations of anti-CII antibodies were undetectable in these mice, whereas they displayed significantly increased concentrations of interferon gamma and interleukin 6. In addition, the CII specific B cell responses in the draining lymph nodes were highly suppressed. Also, mice treated with etoposide at the onset of clinical arthritis showed reduced frequency of their disease by 50%. CONCLUSION: There was a striking disease alleviating impact of topoisomerase II antagonist on the course of CII-induced arthritis.
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| 48. |
- Zare, Fariba, 1972, et al.
(author)
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Arthritogenic properties of double-stranded (viral) RNA
- 2004
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In: J Immunol. - 0022-1767. ; 172:9, s. 5656-63
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Journal article (peer-reviewed)abstract
- Viral infections often lead to arthralgias and overt arthritic states. The inflammatogenic compound of the viruses giving rise to such an outcome has to date not been identified. Because expression of dsRNA is a common feature of all viruses, we decided to analyze whether this property leads to the induction of arthritis. Histological signs of arthritis were evident already on day 3 following intra-articular administration of dsRNA. Arthritis was characterized by infiltration of macrophages into synovial tissue. It was not dependent on acquired immune responses because SCID mice also raised joint inflammation. NF-kappa B was activated upon in vitro exposure to dsRNA, indicating its role in the induction/progression of arthritis. Importantly, we found that dsRNA arthritis was triggered through IL-1R signaling because mice being deficient for this molecule were unable to develop joint inflammation. Although dsRNA is typically recognized by Toll-like receptor 3, Toll-like receptor 3 knockout mice developed arthritis, indicating that some other receptors are instrumental in the inducing of inflammation. Our results from in vitro experiments indicate that proinflammatory cytokines and chemokines stimulating monocyte influx were readily triggered in response to stimulation with dsRNA. These findings demonstrate that viral dsRNA is clearly arthritogenic. Importantly, macrophages and their products play an important role in the development of arthritis triggered by dsRNA.
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