PubMed Central (PMC3 - NLM DTD)
(2,081,148 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 21 - 40 de 420
21.
Mesenchymal precursor cells in the blood of normal individuals - Zvaifler, Nathan J; Marinova-Mutafchieva, Lilla; Adams, Gill; Edwards, Christopher J; Moss, Jill; Burger, Jan A; Maini, Ravinder N
Mesenchymal precursor cells found in the blood (BMPCs) of normal persons adhere to plastic and glass and proliferate logarithmically in DMEM-20% fetal calf serum (FCS) without growth factors. They form cells with fibroblast-like and stromal morphology, which is not affected by eliminating CD34, CD3, or CD14 cells. Osteogenic supplements (dexamethasone, ascorbic acid, and ?-glycerophosphate) added to the culture inhibited fibroblast formation, and BMPCs assumed the cuboidal shape of osteoblasts. After 5 days in supplemented medium, the elutriated cells displayed alkaline phosphatase (AP), and the addition of bone morphogenetic protein (BMP)2 (1 ng) doubled AP production (P < 0.04). Two weeks...
22.
FcgammaR expression on macrophages is related to severity and chronicity of synovial inflammation and cartilage destruction during experimental immune-complex-mediated arthritis (ICA) - Blom, Arjen B; van Lent, Peter L; van Vuuren, Hanneke; Holthuysen, Astrid E; Jacobs, Cor; van de Putte, Leo B; van de Winkel, Jan G; van den Berg, Wim B
We investigated the role of Fc? receptors (Fc?Rs) on synovial macrophages in immune-complex-mediated arthritis (ICA). ICA elicited in knee joints of C57BL/6 mice caused a short-lasting, florid inflammation and reversible loss of proteoglycans (PGs), moderate chondrocyte death, and minor erosion of the cartilage. In contrast, when ICA was induced in knee joints of Fc receptor (FcR) ?-chain-/- C57BL/6 mice, which lack functional Fc?RI and RIII, inflammation and cartilage destruction were prevented. When ICA was elicited in DBA/1 mice, a very severe, chronic inflammation was observed, and significantly more chondrocyte death and cartilage erosion than in arthritic C57BL/6 mice. The synovial...
23.
Enhanced expression of genes involved in coagulation and fibrinolysis in murine arthritis - Salvi, Roberto; Péclat, Veronique; So, Alexander; Busso, Nathalie
We have analyzed the pattern of procoagulant and fibrinolytic gene expression in affected joints during the course of arthritis in two murine models. In both models, we found an increased expression of tissue factor, tissue factor pathway inhibitor, urokinase plasminogen activator, and plasminogen activator inhibitor 1, as well as thrombin receptor. The observed pattern of gene expression tended to favor procoagulant activity, and this pattern was confirmed by functional assays. These alterations would account for persistence of fibrin within the inflamed joint, as is seen in rheumatoid arthritis.
24.
Role of IL-12 in Staphylococcus aureus-triggered arthritis and sepsis - Hultgren, Olof H; Stenson, Martin; Tarkowski, Andrzej
The present study demonstrates that endogenous production of IL-12 is crucial for survival in Staphylococcus aureus-induced arthritis in mice. Staphylococcal load is enhanced in several organs, because of lack of IL-12. This might be due to decreased production of IFN-? in IL-12-deficient mice. Although IL-12-deficient mice were exposed to higher staphylococcal load, they demonstrated no increased severity of arthritis as compared with control animals.
25.
Synovial cytokine mRNA expression during arthritis triggered by CpG motifs of bacterial DNA - Deng, Guo-Min; Tarkowski, Andrej
Our results show that cytokines derived from macrophages play an important role in pathogenesis of arthritis triggered by CpG oligodinucleotide (CpG ODN). IL-12 is in this respect an important immunomodulator during the development of joint inflammation.
26.
Rheumatoid synovial CD4+ T cells exhibit a reduced capacity to differentiate into IL-4-producing T-helper-2 effector cells - Davis, Laurie S; Cush, John J; Schulze-Koops, Hendrik; Lipsky, Peter E
CD4+ memory T cells (Tm) from rheumatoid arthritis peripheral blood (RAPB) or peripheral blood from normal donors produced IL-2, whereas fewer cells secreted IFN-? or IL-4 after a brief stimulation. RAPB Tm contained significantly more IFN-? producers than normal cells. Many rheumatoid arthritis (RA) synovial Tm produced IFN-? alone (40%) and fewer cells produced IL-2 or IL-4. An in vitro model was employed to generate polarized T-helper (Th) effectors. Normal and RAPB Tm differentiated into both IFN-?- and IL-4-producing effectors. RA synovial fluid (RASF) Tm demonstrated defective responsiveness, exhibiting diminished differentiation of IL-4 effectors, whereas RA synovial tissue (RAST) Tm...
27.
The development of clinical signs of rheumatoid synovial inflammation is associated with increased synthesis of the chemokine CXCL8 (interleukin-8) - Kraan, Maarten C; Patel, Dhavalkumar D; Haringman, Jasper J; Smith, Malcolm D; Weedon, Helen; Ahern, Michael J; Breedveld, Ferdinand C; Tak, Paul P
Paired synovial tissue samples were obtained from both clinically uninvolved (CU) and clinically involved (CI) knee joints of eight rheumatoid arthritis (RA) patients. In addition, biopsies were taken from five control subjects. We observed the expression of the chemokines CXCL8, CXCL9, CXCL10, CCL2 and CCL4 in CI and CU joints of RA patients. In particular, CXCL8 protein levels were specifically increased in CI joints compared with CU joints, which was confirmed by immunohistochemistry and in situ hybridization.
28.
Isolation and characterization of rheumatoid arthritis synovial fibroblasts from primary culture primary culture cells markedly differ from fourth-passage cells - Zimmermann, Thomas; Kunisch, Elke; Pfeiffer, Robert; Hirth, Astrid; Stahl, Hans-Detlev; Sack, Ulrich; Laube, Anke; Liesaus, Eckehard; Roth, Andreas; Palombo-Kinne, Ernesta; Emmrich, Frank; Kinne, Raimund W
To reduce culture artifacts by conventional repeated passaging and long-term culture in vitro, the isolation of synovial fibroblasts (SFB) was attempted from rheumatoid arthritis (RA) synovial membranes by trypsin/collagenase digest, short-term in vitro adherence (7 days), and negative isolation using magnetobead-coupled anti-CD14 monoclonal antibodies. This method yielded highly enriched SFB (85% prolyl-4-hydroxylase+/74% Thy-1/CD90+ cells; <2% contaminating macrophages; <1% leukocytes/endothelial cells) that, in comparison with conventional fourth-passage RA-SFB, showed a markedly different phenotype and significantly lower proliferation rates upon stimulation with platelet-derived growth factor and IL-1?. This isolation method is simple and reliable, and may yield cells with features closer to...
29.
Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing MCP-1 and IL-8 - Hayashida, Kenji; Nanki, Toshihiro; Girschick, Hermann; Yavuz, Sule; Ochi, Takahiro; Lipsky, Peter E
Macrophages that accumulate in the synovium of rheumatoid arthritis patients play an important role in the pathogenesis of this inflammatory disease. However, the mechanism by which macrophages are attracted into the inflamed synovium and accumulate there has not been completely delineated. The results of this study show that rheumatoid arthritis synovial stromal cells produce the chemokines monocyte chemotactic protein-1 and IL-8, and these have the capacity to attract peripheral monocytes. These results suggest that one of the mechanisms by which macrophages accumulate in the inflamed synovium is by responding to the chemokines produced locally.
30.
Phenotypic characteristics of human monocytes undergoing transendothelial migration - Grisar, Johannes; Hahn, Philipp; Brosch, Susanne; Peterlik, Meinrad; Smolen, Josef S; Pietschmann, Peter
In our study we characterised the immunophenotype of monocytes that migrated through an endothelial cell (EC) monolayer in vitro. We found that monocyte migration led to an enhanced expression of CD11a, CD33, CD45RO, CD54 [intercellular cell-adhesion molecule (ICAM)-1] and human leucocyte antigen-DR. The most striking increase was observed for ICAM-1 when ECs were activated with tumour necrosis factor-? and interleukin-1?. The results of our study indicate the following: (1) there is a characteristic immunophenotype on the surface of monocytes after transendothelial migration; (2) this phenotype seems to be induced by interactions between monocytes and ECs; and (3) this change is...
31.
IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis - Chabaud, Martine; Lubberts, Erik; Joosten, Leo; van den Berg, Wim; Miossec, Pierre
The origin and role of IL-17, a T-cell derived cytokine, in cartilage and bone destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibited its synthesis. On human RA bone explants, IL-17 also increased bone resorption and decreased formation. Addition of IL-1 in these conditions increased the effect of IL-17. Blocking of bone-derived endogenous IL-17 with specific inhibitors resulted in a protective inhibition of bone destruction. Conversely, intra-articular administration...
32.
Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma) - Scheja, Agneta; Ã?kesson, Anita; Geborek, Pierre; Wildt, Marie; Wollheim, Claes B; Wollheim, Frank A; Vischer, Ulrich M
In 44 consecutive patients with systemic sclerosis (SSc), plasma concentrations of von Willebrand factor (vWf) were higher than those of the vWf propeptide, but the propeptide showed less variability within patient subgroups. Higher values of the propeptide were observed in patients with early pulmonary involvement. A closer correlation of the propeptide than of vWf to biochemical markers of activity was also evident. Our results suggest that the propeptide, despite a shorter circulating half-time and lower plasma concentrations than vWf, is more useful in the assessment of disease activity in SSc.
33.
Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis - Dessein, Patrick H; Joffe, Barry I; Stanwix, Anne E; Moomal, Zubair
Hypothalamicâ??pituitaryâ??adrenal underactivity has been reported in rheumatoid arthritis (RA). This phenomenon has implications with regard to the pathogenesis and treatment of the disease. The present study was designed to evaluate the secretion of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) and its relation to clinical variables in RA, spondyloarthropathy (Spa), and undifferentiated inflammatory arthritis (UIA). Eighty-seven patients (38 with RA, 29 with Spa, and 20 with UIA) were studied, of whom 54 were women. Only 12 patients (14%) had taken glucocorticoids previously. Age-matched, healthy women (134) and men (149) served as controls. Fasting blood samples were taken for determination of the...
35.
Inflammatory microcrystals induce murine macrophage survival and DNA synthesis - Hamilton, John A; McCarthy, Geraldine; Whitty, Genevieve
The interaction of particulates with resident macrophages is a consistent feature in certain forms of crystal-induced inflammation, for example, in synovial tissues, lung, and the peritoneum. The mitogenic activity of basic calcium phosphate (BCP) crystals and calcium pyrophosphate dihydrate (CPPD) crystals on synovial fibroblasts has been considered relevant to the synovial hyperplasia observed in crystal-induced arthritis. The aim of the study was to determine whether microcrystals such as these could enhance macrophage survival and induce DNA synthesis, thus indicating that they may contribute to the tissue hyperplasia.
36.
Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis - Moreland, Larry; Gugliotti, Ron; King, Kevin; Chase, Walter; Weisman, Michael; Greco, Thomas; Fife, Rose; Korn, Joseph; Simms, Robert; Tesser, John; Hillson, Jan; Caldwell, Jacques; Schnitzer, Thomas; Lyons, David; Schwertschlag, Ullrich
Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints.
37.
Autoimmune response to U1 small nuclear ribonucleoprotein (U1 snRNP) associated with cytomegalovirus infection - Newkirk, Marianna M; van Venrooij, Walther J; Marshall, Gary S
The induction of autoantibodies to U1 small nuclear ribonucleoprotein (U1 snRNP) complexes is not well understood. We present evidence that healthy individuals with cytomegalovirus (CMV) infection have an increased frequency and quantity of antibodies to ribonucleoprotein, directed primarily against the U1-70k protein. A significant association between the presence of antibodies to CMV and antibodies to the total RNP targeted by the immune response to the spliceosome (to both the Sm and RNP; Sm/RNP) was found for patients with systemic lupus erythematosus (SLE) but not those with mixed connective-tissue disease. CMV thus may play a role in inducing autoimmune responses in...
38.
Approaches to enhancing the retroviral transduction of human synoviocytes - Del Vecchio, Maria A; Georgescu, Helga I; McCormack, James E; Robbins, Paul D; Evans, Christopher H
This report concerns a clinical trial for rheumatoid arthritis (RA), approved by the US National Institutes of Health and the Food and Drug Administration. An amphotropic retrovirus (MFG-IRAP) was used ex vivo to transfer a cDNA encoding human interleukin-1 receptor antagonist (IL-1Ra) to synovium. The protocol required the transduced cells to secrete at least 30 ng IL-1Ra/106 cells per 48 h before reimplantation. Here we have evaluated various protocols for their efficiency in transducing cultures of human rheumatoid synoviocytes. The most reliably efficient methods used high titer retrovirus (approximately 108 infectious particles/ml). Transduction efficiency was increased further by exposing the...
39.
Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease - Cook, Andrew D; Braine, Emma L; Campbell, Ian K; Rich, Melissa J; Hamilton, John A
There is mounting evidence for a role of the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in inflammatory disease, including arthritis. In the present study, we examined the effectiveness of treatment of collagen-induced arthritis (CIA) with a neutralizing mAb to GM-CSF. DBA/1 mice were immunized for the development of CIA and treated at different times, and with different doses, with neutralizing mAb to GM-CSF or isotype control mAb. Anti-GM-CSF mAb treatment prior to the onset of arthritis, at the time of antigen challenge, was effective at ameliorating the ensuing disease. Modulation of arthritis was seen predominantly as a reduction in overall...
40.
Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus - Graham, Robert R; Langefeld, Carl D; Gaffney, Patrick M; Ortmann, Ward A; Selby, Scott A; Baechler, Emily C; Shark, Katherine B; Ockenden, Theresa C; Rohlf, Kristine E; Moser, Kathleen L; Brown, William M; Gabriel, Sherine E; Messner, Ronald P; King, Richard A; Horak, Pavel; Elder, James T; Stuart, Philip E; Rich, Steven S; Behrens, Timothy W
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families....
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