Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Besides roles in nucleus mediating the condensation of DNA into chromatin, the involvement of histones in autoimmune diseases, hormone regulation, and killing leukemia cells has been reported. In order to investigate the functions of histones on an autoimmune disease, histone H1 was injected into collagen-induced arthritis (CIA) mice. A dramatic suppression of CIA by histone H1 was observed at a dose of 1 mg/kg bodyweight of mouse. In addition, the increased level of anti-inflammatory cytokine IL-10 was detected in cultured splenocytes from the mouse treated with histone H1. These findings suggest that histone H1 suppresses the collagen-induced arthritis, possibly by increasing the level of IL-10 production.
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PMID:Suppression of collagen-induced arthritis with histone H1. 1102 42

Proteoglycan-induced arthritis (PGIA) is a murine model for rheumatoid arthritis (RA) both in terms of its pathology and its genetics. PGIA can only be induced in susceptible mouse strains and their F(2) progeny. Using the F(2) hybrids resulting from an F(1) intercross of a newly identified susceptible (C3H/HeJCr) and an established resistant (C57BL/6) strain of mouse, our goals were to: 1) identify the strain-specific loci that confer PGIA susceptibility, 2) determine whether any pathophysiological parameters could be used as markers that distinguish between nonarthritic and arthritic mice, and 3) analyze the effect of the MHC haplotype on quantitative trait loci (QTL) detection. To identify QTLs, we performed a genome scan on the F(2) hybrids. For pathophysiological analyses, we measured pro- and antiinflammatory cytokines such as IL-1, IL-6, IFN-gamma, IL-4, IL-10, IL-12, Ag-specific T cell proliferation and IL-2 production, serum IgG1 and IgG2 levels of both auto- and heteroantibodies, and soluble CD44. We have identified four new PGIA-linked QTLs (Pgia13 through Pgia16) and confirmed two (Pgia5, Pgia10) from our previous study. All new MHC-independent QTLs were associated with either disease onset or severity. Comprehensive statistical analysis demonstrated that while soluble CD44, IL-6, and IgG1 vs. IgG2 heteroantibody levels differed significantly between the arthritic and nonarthritic groups, only Ab-related parameters colocalized with the QTLs. Importantly, the mixed haplotype (H-2(b) and H-2(k)) of the C3H x C57BL/6 F(2) intercross reduced the detection of several previously identified QTLs to suggestive levels, indicating a masking effect of unmatched MHCs.
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PMID:A genome scan using a novel genetic cross identifies new susceptibility loci and traits in a mouse model of rheumatoid arthritis. 1104 62

IL-10, IL-13, IFN-gamma, tumor necrosis factor (TNF)-alpha, LT-alpha, CD154, and TNF-related activation-induced cytokine (TRANCE) were expressed by 2-20% of rheumatoid arthritis (RA) synovial tissue CD4(+) memory T cells, whereas CD4(+) cells that produced IL-2, IL-4, or IL-6 were not detected. Expression of none of these molecules by individual CD4(+) cells correlated with the exception of TRANCE and IL-10, and TRANCE and TNF-alpha. A correlation between expression of IL-10 and CCR7, LT-alpha and CCR6, IFN-gamma and CCR5, and TRANCE and CXCR4 was also detected.
Arthritis Res 2000
PMID:Cytokine, activation marker, and chemokine receptor expression by individual CD4(+) memory T cells in rheumatoid arthritis synovium. 1105 76

For the treatment of rheumatoid arthritis, efficient drug delivery methods to the inflamed joints need to be developed. Because T cells expressing an appropriate autoantigen-specific receptor can migrate to inflamed lesions, it has been reasoned that they can be employed to deliver therapeutic agents. To examine the ability and efficiency of such T cells as a vehicle, we employed an experimentally induced model of arthritis. Splenic T cells from DO11.10 TCR transgenic mice specific for OVA were transduced with murine IL-10. Adoptive transfer of the IL-10-transduced DO11.10 splenocytes ameliorated OVA-induced arthritis despite the presence of around 95% nontransduced cells. Using green fluorescent protein as a marker for selection, the number of transferred cells needed to ameliorate the disease was able to be reduced to 10(4). Preferential accumulation of the transferred T cells was observed in the inflamed joint, and the improvement in the disease was not accompanied by impairment of the systemic immune response to the Ag, suggesting that the transferred T cells exert their anti-inflammatory task locally, mainly in the joints where the Ag exists. In addition, IL-10-transduced DO11.10 T cells ameliorated methylated BSA-induced arthritis when the arthritic joint was coinjected with OVA in addition to methylated BSA. These results suggest that T cells specific for a joint-specific Ag would be useful as a therapeutic vehicle in rheumatoid arthritis for which the arthritic autoantigen is still unknown.
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PMID:Antigen-specific T cells transduced with IL-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen. 1106 61

Previously we have shown that T cell responses to the mycobacterial 60-kDa heat shock protein (hsp60) peptide M256-270 mediated protection against adjuvant arthritis in Lewis rats. We have demonstrated now that M256-270-primed T cells become highly reactive to naive syngeneic APC upon repetitive restimulation in vitro with peptide M256-265, comprising the conserved core of peptide M256-270. These autoproliferative responses in the absence of added Ag were MHC class II restricted and resulted in the production of IL-4/IL-10 and IFN-gamma. Enhanced autoproliferation and expression of the cell surface molecule B7.2 by these T cells were observed in response to syngeneic heat-shocked APC, which indicated that the autoproliferation and expression of B7.2 resulted from the recognition of endogenously expressed and processed hsp. Despite their strong autoreactivity, upon transfer such T cells were found to induce a significant disease reduction in adjuvant arthritis. In contrast, T cells both primed and restimulated with peptide M256-270 became unresponsive toward syngeneic APC as well as toward the conserved core peptide M256-265, and they were devoid of protective capacity. This study demonstrates that the loss of self-tolerance toward hsp60 does not necessarily lead to autoimmune disease, but that hsp60-specific self-reactive and autoproliferative T cells may mediate T cell regulation in arthritis.
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PMID:Highly autoproliferative T cells specific for 60-kDa heat shock protein produce IL-4/IL-10 and IFN-gamma and are protective in adjuvant arthritis. 1112 Aug 61

The major, extensively studied, experimentally-induced rat and mouse models of arthritis with features resembling rheumatoid arthritis are reviewed here. Etiopathogenetic studies that were recently published are emphasized. In summary, multiple triggering stimuli can induce disease in genetically-prone strains of inbred rats and mice. Multiple genetic loci, including both MHC and non-MHC, regulate disease expression in these animals. By comparison with other models of autoimmune disease, clustering of regulatory loci within and among species is increasingly becoming evident. At the cellular level, both innate and acquired immune systems are involved in the disease manifestations. At the molecular level, unbalanced chronic production of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-6 and IL-12, as opposed to IL-4 and IL-10, is correlated with arthritis disease susceptibility and severity.
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PMID:Animal models of rheumatoid arthritis and related inflammation. 1112 28

The assessment of cytokines and their soluble receptors in the synovial fluid (SF) of inflammatory arthropathies may be useful in studying pathogenetic and immunoregulatory mechanisms underlying different diseases. The aim of this work was to study the cytokine network occurring in inflammatory arthropathies and to identify a cytokine profile which is characteristic of an immune-mediated synovitis. Levels of IL-12, as well as IL-4, IL-8, IL-10, IFN-gamma, sCD25, TNF-alpha and its soluble receptors were measured in the SF of various arthropathies, i.e. non-inflammatory arthropathies: "control" meniscus pathology (n = 21), osteoarthritis (n = 22) and chronic crystal arthritis (n = 9); a non-immune inflammatory arthropathy: acute crystal arthritis (n = 11); 2 immune inflammatory arthropathies: reactive arthritis (ReA) (n = 23) and rheumatoid arthritis (RA) (n = 44). SF levels of IL-10, TNF-alpha and sTNF-RII were found to be increased in the three inflammatory arthropathies compared to the "control" meniscus group. Within the inflammatory group, acute crystal arthritis was characterized by a significantly higher sTNF-RI/TNF-alpha ratio and ReA by a significantly lower sTNF-RII/TNF-alpha ratio compared to the two other diseases. The two immune arthropathies, RA and ReA, were characterized by increased SF levels of IL-12, sCD25 and of the sTNF-RII/sTNF-RI ratio. ReA differed however from RA by showing lower IL-8 and IL-4 levels, higher IFN-gamma levels and a higher IL-12/IL-10 ratio, suggesting a more prevalent Th1 profile in ReA SF. Our data indicate that the measurement of SF cytokines and soluble receptors may discriminate between each inflammatory arthropathy and might be useful in clinical practice.
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PMID:Increased synovial fluid levels of interleukin-12, sCD25 and sTNF-RII/sTNF-RI ratio delineate a cytokine pattern characteristic of immune arthropathies. 1112 12

Collagen-induced arthritis is an animal model of inflammatory polyarthritis that is induced in susceptible strains of rats and mice by intradermal immunization with heterologous type II collagen emulsified in complete Freund's adjuvant. Previous studies have demonstrated that disease induction is highly MHC-restricted, with only mice of H-2(q) or H-2(r) haplotypes being susceptible. We have used a panel of both susceptible and resistant strains of mice in which either IFN-gamma or IL-10 signaling has been abolished by gene deletion and show that disease can be readily induced in several resistant strains of the H-2(b) and H-2(d) haplotype; susceptibility was highly dependent on IL-12. IL-4 was also shown to be crucial for disease induction in this model. These results suggest that both Th1 and Th2 cytokines may be important in the etiopathogenesis of disease and that disease susceptibility may be a function of a dysregulated cytokine environment.
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PMID:Susceptibility to collagen-induced arthritis: cytokine-mediated regulation. 1114 33

The basis of the different susceptibility to bacterial cell wall-induced arthritis between Lewis and Fischer rats is unclear. Likewise, it is not known why cell walls of some species of Lactobacillus are arthritogenic and those of others are not. With these two questions in mind, we investigated the role of anti-inflammatory (interleukin (IL)-10, IL-4) and proinflammatory (tumour necrosis factor (TNF)-alpha, IL-1 beta) cytokines in Lewis and Fischer rats injected intraperitoneally with cell walls from arthritogenic or nonarthritogenic species of Lactobacillus. Cytokine levels in the serum and in vitro production by peritoneal macrophages and splenocytes were studied. The results obtained indicate that the differences in the production of IL-10, IL-4, TNF-alpha or IL-1 beta do not explain the difference in the arthritis susceptibility between Lewis and Fischer rats. Likewise, the arthritogenicity of different Lactobacillus cell walls appears not to be dependent on their capacity to stimulate cytokine production.
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PMID:Cytokine production in arthritis susceptible and resistant rats: a study with arthritogenic and non-arthritogenic Lactobacillus cell walls. 1116 16

For the treatment of rheumatoid arthritis, efficient drug delivery methods to the inflamed joints need to be developed. Since T cells expressing an appropriate autoantigen-specific receptor can migrate to inflamed lesions, it has been reasoned that they can be employed to deliver therapeutic agents. In order to examine the ability and efficiency of such T cells as a vehicle, we employed an experimentally induced model of arthritis. Splenic T cells from DO 11.10 T cell receptor transgenic mice specific for OVA were transduced with murine IL-10. Adoptive transfer of the IL-10-transduced DO 11.10 splenocytes ameliorated OVA-induced arthritis, in spite of the presence of around 95% non-transduced cells. Using GFP as a marker for selection, the number of transferred cells needed to ameliorate the disease was able to be reduced to 10(4). Preferential accumulation of the transferred T cells was observed in the inflamed joint, and the improvement in the disease was not accompanied by impairment of the systemic immune response to the antigen, suggesting that the transferred T cells exert their antiinflammatory task locally, mainly in the joints where the antigen exists. In addition, IL-10-transduced DO 11.10 T cells ameriolated mBSA-induced arthritis when the arthritic joint was co-injected with OVA in addition to mBSA. These results suggest that T cells specific for a joint specific antigen would be useful as a therapeutic vehicle in rheumatoid arthritis for which the arthritic autoantigen is still unknown.
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PMID:[Antigen-specific T cells transduced with interleukin-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen]. 1121 Jul 37


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