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)

This study reports on leukemia inhibitory factor (LIF) in human articular connective tissues. Biologically active LIF is present in synovial fluids from patients with osteoarthritis and at higher titers in samples from patients with rheumatoid arthritis. Cultured human synoviocytes and articular chondrocytes produced biologically active LIF and synthesized and secreted LIF proteins that migrated in SDS PAGE at approximately 43 kD. This was increased after stimulation with IL-1 beta. Chondrocytes in serum-containing cultures expressed the 4.2-kb LIF mRNA. IL-1 beta, LPS, and to a lesser extent tumor necrosis factor-alpha induced LIF gene expression. LIF autoinduced its mRNA and this provides evidence for an effect of this cytokine on function of joint tissue cells. Among a series of growth factors tested, transforming growth factor (TGF beta), including the isoforms TGF-beta1, TGF-beta 2, and TGF-beta 3, platelet-derived growth factor, basic fibroblast growth factor, and insulin-like growth factor induced this cytokine gene but differed with respect to the duration of their effects. Cultured synoviocytes expressed the LIF gene in response to the same set of peptide regulatory factors. Analysis of signal transduction pathways showed that PMA increased LIF mRNA, whereas calcium ionophore and cAMP had no detectable effects. Cycloheximide was a potent LIF mRNA inducer and dexamethasone inhibited LIF induced by PMA or IL-1 beta. Cartilage organ cultures and synovial tissues stimulated with IL-1 expressed high levels of LIF mRNA as demonstrated by in situ hybridization. These results identify LIF as a new cytokine that is produced by joint tissue cells and is overexpressed in arthritis. The induction of this cytokine by factors that are present during joint inflammation and the effects of LIF on connective tissue cells suggest that LIF is a mediator that can contribute to the pathogenesis of arthritis.
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PMID:Leukemia inhibitory factor is expressed in cartilage and synovium and can contribute to the pathogenesis of arthritis. 152 40

We examined whether tumour necrosis factor (TNF) or transforming growth factor-beta 1 (TGF-beta 1) could alter the course of collagen-induced arthritis (CIA). Injection of 100 ng TNF or 500 ng TGF-beta 1 into ankle joints of normal rats induced a very limited inflammatory response, observable only upon histological analysis. However, when injected into ankle joints of rats 9 days after immunization with bovine type II collagen (CII), identical doses of TNF or TGF-beta 1 induced a sustained, clinically obvious inflammation and oedema that began within 8 h on average, as compared to 90 h in CII-immunized control rats given no injections or intra-articular injections of buffer. The incidence of arthritis at 2 weeks post-immunization was 100% for TNF-injected hindpaws, compared with 55% for the control groups, a statistically significant difference. In rats passively immunized with a subarthritic dose of affinity purified antibody to rat-CII, intra-articular injection of 100 ng TNF or 500 ng of TGF-beta 1 also induced intense, though transient arthritis. The rapid proinflammatory effects in CIA described in this study and the synergy demonstrated between anti-CII IgG and either cytokine, suggest that these cytokines can participate locally in the pathogenesis of arthritis.
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PMID:Acceleration of onset of collagen-induced arthritis by intra-articular injection of tumour necrosis factor or transforming growth factor-beta. 163 67

Bacterial cell wall-induced arthritis in experimental animals is dependent on mononuclear cell infiltration and accumulation. These mononuclear cells secrete cytokines which promote synovial hyperplasia and erosive destruction of bone and cartilage. Whereas local administration of cytokines may exacerbate these events, systemic administration of TGF-beta or gamma IFN effectively suppresses both the acute and chronic phases of the disease.
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PMID:Cytokine modulation of bacterial cell wall-induced arthritis. 178 21

Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute to the inflammatory response associated with autoimmune diseases. Transforming growth factor beta 1 (TGF-beta 1) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown that microgram amounts of TGF-beta 1, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) and relapsing experimental allergic encephalomyelitis (REAE), the animal models for rheumatoid arthritis and multiple sclerosis, respectively. When administered during induction of the disease, TGF-beta 1 prevents CIA but only delays the onset of REAE by 2-3 days. However, when administered during a remission. TGF-beta 1 prevents the occurrence of relapses in REAE. The results suggest that TGF-beta 1 has powerful anti-inflammatory effects, mimicking in some respects the beneficial effects of immunosuppressive drugs in these experimental models of autoimmune disease, but without discernable adverse effects.
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PMID:Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. 201

Paracrine growth factors probably stimulate the pathologic proliferation of synovial fibroblast-like cells (synoviocytes) in rheumatoid arthritis (RA), but the relative importance of various factors is highly controversial. To address this problem, we compared the effects of highly purified or recombinant cytokines, in serum-free medium, on the in vitro long-term growth of synoviocytes from patients with RA and rats with streptococcal cell wall (SCW) arthritis. Of the factors tested (PDGF, aFGF, bFGF, EGF, TGF-beta, IL-1-alpha, TNF-alpha and IFN-gamma), PDGF, was clearly the most potent stimulant of long-term growth of both rat and human synoviocytes. The strong mitogenic activity of rheumatoid synovial fluids was significantly inhibited by neutralizing anti-PDGF antibody, thus confirming the importance of PDGF. EGF, TGF-beta, IL-1-alpha, TNF-alpha, and IFN-gamma had minimal effects. Similar to the effects on anchorage-independent growth, TGF-beta 1 and 2, inhibited serum- or PDGF-stimulated anchorage-dependent growth. Considered in the context of other reports, these data support the view that cytokines such as PDGF, and possibly aFGF and bFGF, play major roles in stimulating synoviocyte hyperplasia in RA and SCW arthritis, whereas TGF-beta may inhibit synoviocyte growth.
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PMID:Cytokines and growth regulation of synoviocytes from patients with rheumatoid arthritis and rats with streptococcal cell wall arthritis. 218 94

After intraarticular injection of TGF-beta 1 or TGF-beta 2, marked swelling and erythema of the injected joints were apparent within 12-24 h. On a scale of 0 to 4, by day 3, the TGF-beta-treated joints had articular indices (AI) of 3.6 +/- 0.5 to 4.0 +/- 0.0 compared with no response for the vehicle-injected contralateral joints. Histopathologic evaluation revealed a predominantly mononuclear phagocyte infiltrate with some neutrophils and T lymphocytes, consistent with active inflammation. The monocytic pattern of leukocyte infiltration at 2-3 d was comparable to that seen in animals with antigen-induced arthritis after 2-3 wk. Extensive synovial fibroblast hyperplasia became apparent within 48 h, likely as a result of TGF-beta induction of growth factor synthesis by the accumulating monocytes. TGF-beta 2, a homologue of TGF-beta 1, was found to induce a similar level of synovitis and synovial hyperplasia consistent with its parallel monocyte and fibroblast chemotactic properties and ability to induce transcription and translation of monocyte/macrophage-derived growth factors. These data suggest that TGF-beta, released by platelets and activated inflammatory cells, may play a direct role in leukocyte recruitment and activation in arthritic and other chronic inflammatory lesions.
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PMID:Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta. 229 77

The growth of synovial fibroblast-like cells from patients with rheumatoid arthritis and rats with streptococcal cell wall (SCW)-induced arthritis in vitro under anchorage-independent conditions is inhibited by transforming growth factor-beta (TGF-beta). Because this growth factor is present in rheumatoid synovial fluids, we studied whether this cytokine might be secreted by cells in rheumatoid synovial tissue. We show that synovial tissues from patients with rheumatoid arthritis and osteoarthritis, and rats with SCW-induced arthritis, contain TGF-beta-1 mRNA. TGF-beta, predominantly type 1, was spontaneously secreted in vitro by synovial tissue explants and synovial fibroblast-like cells. In addition, TGF-beta could be detected immunohistochemically in cells throughout rheumatoid and SCW-induced arthritic rat synovial tissues. Finally, exogenous TGF-beta induced collagen and inhibited collagenase mRNA levels by cultured synoviocytes. These data support an autocrine role for TGF-beta in the regulation of synoviocytes in rheumatoid arthritis and, in light of its demonstrated effects on the immune system, suggest that TGF-beta might also have important paracrine effects on infiltrating inflammatory cells.
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PMID:Transforming growth factor-beta production by synovial tissues from rheumatoid patients and streptococcal cell wall arthritic rats. Studies on secretion by synovial fibroblast-like cells and immunohistologic localization. 266 90

We tested the hypothesis that normal synovial fibroblasts might proliferate in response to transforming growth factors (TGFs), peptides that are extracted with acid-ethanol from bovine kidney or salivary gland and that cause anchorage-independent growth of normal cells. A 72-hour exposure of confluent monolayers of rabbit synovial fibroblasts in 10% fetal calf serum to partially purified TGF-beta in the presence of TGF-alpha gave a 2- to 5-fold increase in incorporation of 3H-thymidine, protein content, and cell number. Similar results were obtained with high pressure liquid chromatography-purified TGF-beta in the presence of epidermal growth factor (EGF) (a type of TGF-alpha). By itself, purified TGF-beta was not mitogenic; it depended absolutely on EGF. However, only TGF-beta along with EGF, and not EGF alone, induced a marked morphologic change: a piling up of cells into foci resembling those commonly seen in primary cultures of rheumatoid synovial cells. Mitogenic responses induced by the TGF-beta-EGF combination were prevented by all-trans-retinoic acid but not by indomethacin or dexamethasone. The data indicate that TGF-beta, a peptide extracted from normal cells, can act in concert with EGF to cause proliferation and piling up of synovial cells and raise the possibility that these factors may play a role in rheumatoid arthritis and other proliferative but nonmalignant diseases as well.
Arthritis Rheum 1983 Nov
PMID:Morphologic and mitogenic responses of rabbit synovial fibroblasts to transforming growth factor beta require transforming growth factor alpha or epidermal growth factor. 631 22

In years to come, new therapeutic modalities for the treatment of chronic arthritis will be launched for general clinical use. These therapies, until today only used in clinical studies, are based on knowledge obtained from animal models of chronic arthritis. This knowledge not only ushers therapeutic use in humans: in many settings, the animal studies have proven to be irreplacable tools to get insights into the pathogenesis of chronic arthritis. Rheumatoid arthritis (RA) shows a strong linkage of susceptibility to a certain epitope common to some HLA-DR beta chains; this immunogenetic linkage is the strongest evidence for specific, T-cell dependent immunity in the pathogenesis of the disease. Despite intense efforts, no unequivocal proofs of T-cell specificity or oligoclonality have been found in RA. Therapeutic efforts directed against T-cells or T-cell functions have also at the best showed partial effects. As compared to the local production of T-cell cytokines in the joint, monokine production is abundant. Therapies aimed at neutralizing the effects of the cartilage-devastating monokine TNF-a have showed remarkable results in small clinical trials. The possibility of increasing the presence of the regulatory cytokines IL-4, IL-10 and TGF-beta has also been explored, but only in animal studies. Immunology has also shed light on the mode of action of the commonly used 'disease modifying' drugs, and combinations of such drugs have shown increased potentials in recent clinical studies. The possibility of combining traditional anti-arthritic drugs with recent immunological tools seem promising for the future. This review discusses recent advances in the understanding of pathogenesis and delineate new therapeutic approaches for chronic arthritis from the point of view of the immunologically oriented clinician.
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PMID:Immunopathogenesis and immunotherapy in rheumatoid arthritis: an area in transition. 767 48

OT is a relevant biological pathway for generating peripheral tolerance against both self and external antigens with minimal side effects (fig. 3). This route might, therefore, contain promising potential for the treatment of autoimmune and allergic diseases in the human (fig. 3). Thus, oral administration of autoantigens suppresses experimental autoimmune diseases (EAE, EAU, AA, collagen-induced arthritis, NOD diabetes) in a disease- and antigen-specific manner, and oral administration of alloantigens has led to increase of allograft survival. OT might be important in treatment of immune complex diseases and food allergies. OT is mediated by T lymphocytes using at least two nonmutually exclusive mechanisms: suppression and anergy. Suppression can be adoptively transferred by CD8+ T lymphocytes which act by releasing TGF-beta and IL-4 following antigen-specific triggering. Antigen-driven tissue-directed suppression occurs following oral administration of an antigen from the target organ, even if it is not the disease-inducing antigen (bystander suppression). Thus, synthetic peptides can induce OT, and tolerogenic epitopes of antigen may be different from the autoreactive epitope. Due to the promising results in animal models, OT is being tested in clinical trials in multiple sclerosis, rheumatoid arthritis and uveitis [193, 194].
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PMID:Oral tolerance: a biologically relevant pathway to generate peripheral tolerance against external and self antigens. 801 Nov 55


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