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)

Ten patients with chronic inflammatory arthropathy and the human T lymphotropic virus type I (HTLV-I) are described. These patients showed chronic persistent oligoarthritis, associated with proliferative synovitis, in large joints. The place of birth or residence of these patients was within the area endemic for adult T cell leukemia (ATL) and HTLV-I. The age at onset of articular symptoms tended to be higher in these patients than in typical rheumatoid arthritis patients. Anti-HTLV-I antibodies were detected in both sera and synovial fluids from all patients. Western blot analysis revealed antibodies to viral gag proteins (p19, p24, and p28). Atypical lymphocytes with nuclear indentations, consistent with ATL-like cells, were observed in both synovial fluid and synovial tissue. Furthermore, HTLV-I proviral DNA was integrated into the DNA of synovial fluid cells and synovial tissue cells. These findings suggest that HTLV-I might be involved in the pathogenesis of this unique arthropathy.
Arthritis Rheum 1991 Jun
PMID:Arthritis in patients infected with human T lymphotropic virus type I. Clinical and immunopathologic features. 205 17

The synthesis of caprine arthritis-encephalitis virus structural proteins was analysed in infected cells labelled with [35S]methionine and [3H]glucosamine and by translation of virion RNA in vitro. Viral polypeptides were isolated from infected cell lysates or from in vitro translation products by immunoprecipitation with specific antisera and resolved by SDS-PAGE. Results indicated that the gag gene-encoded p28, p19 and p16 virion core proteins were formed by cleavage processing of a 55K Mr precursor with several intermediate polypeptides. The gp135 virion surface glycoprotein, encoded by the env gene, was formed by post-translational modification of a glycosylated precursor of 150K apparent Mr. This precursor was formed by glycosylation of a 90K primary env gene product.
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PMID:Precursor polypeptides of caprine arthritis-encephalitis lentivirus structural proteins. 335 81

We have identified a Japanese patient with adult T-cell leukemia (ATL) whose T cells in vitro produced the human T-cell leukemia virus (HTLV). This patient presented with lymphomatous arthritis and leukemia and subsequently developed skin lesions. Skin invasion by malignant T-cells was angiocentric and produced vessel wall destruction, resulting in necrotic cutaneous tumor nodules. Malignant T cells in peripheral blood, skin, and joint prior to culture in vitro did not express p19 HTLV-associated antigen. However, by electron microscopy, intracellular type C viral particles were seen in skin-infiltrating T cells. Peripheral blood malignant cells after 7 days in culture with T-cell growth factor-supplemented media expressed p19 antigen, and type C virus particles were seen by electron microscopy to be budding from malignant T lymphocytes. Mitomycin-C-treated peripheral-blood T cells induced the transformation of cord blood T cells into HTLV-infected p19+ T cells. The demonstration of HTLV in malignant T cells from our patient confirms the association of HTLV with Japanese adult T-cell leukemia. Moreover, HTLV may be associated with a vasculitis-arthritis syndrome.
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PMID:Identification of human T cell leukemia virus in a Japanese patient with adult T cell leukemia and cutaneous lymphomatous vasculitis. 660 Dec 76

Interleukin (IL) 23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 affects memory T cell and inflammatory macrophage function through engagement of a novel receptor (IL-23R) on these cells. Recent analysis of the contribution of IL-12 and IL-23 to central nervous system autoimmune inflammation demonstrated that IL-23 rather than IL-12 was the essential cytokine. Using gene-targeted mice lacking only IL-12 (p35-/-) or IL-23 (p19-/-), we show that the specific absence of IL-23 is protective, whereas loss of IL-12 exacerbates collagen-induced arthritis. IL-23 gene-targeted mice did not develop clinical signs of disease and were completely resistant to the development of joint and bone pathology. Resistance correlated with an absence of IL-17-producing CD4+ T cells despite normal induction of collagen-specific, interferon-gamma-producing T helper 1 cells. In contrast, IL-12-deficient p35-/- mice developed more IL-17-producing CD4+ T cells, as well as elevated mRNA expression of proinflammatory tumor necrosis factor, IL-1beta, IL-6, and IL-17 in affected tissues of diseased mice. The data presented here indicate that IL-23 is an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12 paradoxically mediates protection from autoimmune inflammation.
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PMID:Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. 1466 8

IL-23 is regarded as a major pro-inflammatory mediator in autoimmune disease, a role which until recently was ascribed to its related cytokine IL-12. IL-23, an IL-12p40/p19 heterodimeric protein, binds to IL-12Rbeta1/IL-23R receptor complexes. Mice deficient for p19, p40 or IL-12Rbeta1 are resistant to experimental autoimmune encephalomyelitis or collagen-induced arthritis. Paradoxically, however, IL-12Rbeta2- and IL-12p35-deficient mice show remarkable increases in disease susceptibility, suggesting divergent roles of IL-23 and IL-12 in modulating inflammatory processes. IL-23 induces IL-17, which mediates inflammation and tissue remodeling, but the role of IL-12 in this respect remains unidentified. We investigated the roles of exogenous (recombinant) and endogenous (macrophage-derived) IL-12 and IL-23, on IL-17-induction in human T-cells. IL-23 enhanced IL-17 secretion, as did IL-2, IL-15, IL-18 and IL-21. In contrast, IL-12 mediated specific inhibition of IL-17 production. These data support the role of IL-23 in inflammation through stimulating IL-17 production by T lymphocytes, and importantly indicate a novel regulatory function for IL-12 by specifically suppressing IL-17 secretion. These data therefore extend previous reports that had indicated unique functions for IL-23 and IL-12 due to distinct receptor expression and signal transduction complexes, and provide novel insights into the regulation of immunity, inflammation and immunopathology.
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PMID:Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. 1648 11

IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4(+) T cells and stimulating the proliferation of memory CD4(+) T cells. We investigated the pathogenic role of IL-23 in CD4(+) T cells in mice lacking the IL-1R antagonist (IL-1Ra(-/-)), an animal model of spontaneous arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra(-/-) mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly accelerated this joint inflammation and joint destruction. IL-1beta further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4(+) T cells of IL-1Ra(-/-) mice. Blocking IL-23 with anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte cultures. The process of IL-23-induced IL-17 production in CD4(+) T cells was mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-kappaB, whereas p38 MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory cytokine in the pathogenesis of this IL-1Ra(-/-) model of spontaneous arthritis. Its intracellular signaling pathway could be useful therapeutic targets in the treatment of autoimmune arthritis.
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PMID:STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. 1662 35

Although IL-12 and IL-23 share the common p40 subunit, IL-23, rather than IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease. In contrast, we describe in this study that newly created LacZ knockin mice deficient for IL-23 p19 were highly susceptible for the development of experimental T cell-mediated TNBS colitis and showed even more severe colitis than wild-type mice by endoscopic and histologic criteria. Subsequent studies revealed that dendritic cells from p19-deficient mice produce elevated levels of IL-12, and that IL-23 down-regulates IL-12 expression upon TLR ligation. Finally, in vivo blockade of IL-12 p40 in IL-23-deficient mice rescued mice from lethal colitis. Taken together, our data identify cross-regulation of IL-12 expression by IL-23 as novel key regulatory pathway during initiation of T cell dependent colitis.
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PMID:Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. 1692 Sep 9

Recent studies demonstrated an IL-17-producer CD4+ T cell subpopulation, termed Th17, distinct from Th1 and Th2. It represents a different pro-inflammatory Th-cell lineage. This notion is supported by gene-targeted mice studies. Mice lacking IL-23 (p19-/-) do not develop experimental autoimmune encephalomyelitis (EAE) or collagen-induced arthritis (CIA), while knockout mice for the Th1 cytokine IL-12 (p35-/-) strongly develop both autoimmune diseases. Disease resistance by IL-23 knockout mice correlates well with the absence of IL-17-producing CD4(+) T lymphocytes in target organs despite normal presence of antigen-specific-IFN-gamma-producing Th1 cells. This finding may thus explain previous contradictory reports showing that anti-IFN-gamma-treated mice, IFN-gamma- or IFNR-deficient mice develop CIA or EAE. TGF-beta, IL-6 and IL-1 are the differentiation factors of Th17 cells. IL-23 is dispensable for this function, but necessary for Th17 expansion and survival. The master regulator that directs the differentiation program of Th17 cells is the orphan nuclear receptor RORgammat. IL-27, a member of the IL-12/IL-23 family, potently inhibits Th17 development. Evidence suggesting rheumatoid arthritis and multiple sclerosis as primarily IL-17 autoimmune inflammatory-mediated diseases is rapidly accumulating. The IL-17/23 axis of inflammation and related molecules may rise as therapeutic targets for treating these and perhaps other autoimmune diseases.
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PMID:Autoimmune inflammation from the Th17 perspective. 1728 53

Proinflammatory cytokine IL-23 but not IL-12 is critical for the pathogenesis of organ-specific autoimmune diseases including experimental autoimmune encephalitis and collagen-induced arthritis. The contribution by IL-23 in systemic autoimmune diseases such as lupus is undefined. We addressed this question in a murine lupus-like disease model, initiated by enforced cell-surface expression of an ER HSP gp96 in C57BL/6 background. We found a significant increase of p40 in the sera in these mice that preceded the onset of diseases. However, autoimmunity was abrogated in transgenic mice expressing membrane-bound gp96 reconstituted with p35-/- BM, but not with p19-/- BM. Moreover, we found that dendritic cells (DC) but not macrophages were the main producers of p40. To dissect the roles of DC further, we depleted DC using a diphtheria toxin-based inducible DC depletion system. We demonstrated that the integrity of DC was essential for autoimmunity. Our results thus revealed that IL-12 and DC are critical for the pathogenesis of lupus-like disease precipitated by cell surface gp96. This study further highlighted the significant biological differences between IL-12 and IL-23.
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PMID:Essential roles of IL-12 and dendritic cells but not IL-23 and macrophages in lupus-like diseases initiated by cell surface HSP gp96. 1729 5

Considerable effort has been made to elucidate the mechanism of Lyme arthritis. We focused on p19, a cell cycle-regulating molecule, because it is known to inhibit cell cycle division of T lymphocytes which may be responsible for the induction of arthritis. We show that anti-p19 antibody treatment enhances the inflammatory response normally detected at the tibiotarsal joints of Borrelia burgdorferi-vaccinated and Borrelia bissettii-challenged mice. Specifically, anti-p19 antibody treatment augmented the severity of inflammation within the synovial and subsynovial tissue. Moreover, treatment with anti-p19 antibody caused severe erosion of cartilage and bone with ankle joint destruction. In addition, anti-p19 antibody treatment of Borrelia-vaccinated and -challenged mice enhanced the borreliacidal antibody response, especially against the vaccine isolate. The novel activities of anti-p19 antibody show that p19 may be an important therapeutic site for the treatment of Lyme arthritis.
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PMID:Anti-p19 antibody treatment exacerbates lyme arthritis and enhances borreliacidal activity. 1736 Aug 56


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