Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were designed to test the hypothesis that chronic exposure to tumor necrosis factor alpha (TNF) alters the function of activated T lymphocytes. Pretreatment of tetanus toxoid-specific T cell clones with TNF for up to 16 d impaired rechallenge proliferative responses to antigen in a dose- and time-dependent fashion. IL-2 and PHA responses were preserved. Prolonged treatment with TNF impaired production of IL-2, IL-10, IFN gamma, TNF, and lymphotoxin (LT) following stimulation with immobilized OKT3, and resulted in suboptimal expression of the IL-2R alpha chain (Tac) but not CD3, CD4, or HLA-DR antigens, when compared to untreated control cells. By contrast, pretreatment of T cells for prolonged periods in vitro with neutralizing anti-TNF monoclonal antibodies (mAb) enhanced proliferative responses, increased lymphokine production, and upregulated Tac expression following stimulation with OKT3. To determine whether TNF exerts immunosuppressive effects on T cells in vivo, we studied cell-mediated immunity in patients with active rheumatoid arthritis (RA), before and after treatment with a chimeric anti-TNF mAb. Treatment with anti-TNF restored the diminished proliferative responses of PBMC to mitogens and recall antigens towards normal in all patients tested. These data demonstrate that persistent expression of TNF in vitro and in vivo impairs cell-mediated immune responses.
 ...
PMID:Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis. 804 Mar 30

Cytofluorometric analysis was performed to characterize the immunophenotype of lymphocytes of the synovial fluid (SF) and the peripheral blood (PB) from patients suffering from juvenile chronic arthritis (JCA) or rheumatoid arthritis (RA). The most obvious difference could be found in expression of the surface protease aminopeptidase N (AP N/CD13). Whereas monoclonal antibodies specific to CD13 failed to reveal surface expression on lymphocytes of the PB; 63 +/- 15% of SF T cells gave positive staining for CD13 using Leu-M7. No correlation between CD13 expression and joint disease could be found in patients who had different types of inflammatory joint effusions. CD13 expression of T cells was also found in synovial tissue and inflammatory serous cavity effusions. Fixation of T cells revealed the presence of intracellular CD13 antigen already located in the PB T cells of healthy individuals. Induction of CD13 expression on PB T cells could be demonstrated after incubation with Con A/IL-2 or SF from patients with RA. Our findings suggest a role for AP N as a new activation-associated molecule of T lymphocytes.
 ...
PMID:Demonstration of CD13/aminopeptidase N on synovial fluid T cells from patients with different forms of joint effusions. 809 41

Mast cell synovial hyperplasia can occur in patients with rheumatoid arthritis. Histamine can accelerate synovitis and heparin can inhibit lymphocyte function. Since interleukin-4 (IL-4) can stimulate murine mast cell and IgE synthesis, we determined whether mast cell mediators and anti-IL-4 might effect lymphocyte proliferation from patients with rheumatoid arthritis. Twenty-four patients with rheumatoid arthritis and nine normal controls were evaluated by history, physical examination, physician and patient-assessed joint and allergic symptoms, and diary scores. An IL-2-driven-T cell (3H) Tdr proliferation assay with monoclonal anti-IL-4 and a sensitive ELISA were performed with isolated peripheral blood mononuclear cells (PBMC) with 10 micrograms/mL of either concanavalin A (Con A), type I human collagen, or heparin and 10(-6) M histamine. Increased lymphocyte proliferation indices with Con A (mean 21.69 +/- 4.9; 6.54 +/- 3.2 normal controls), type I human collagen (mean 2.17 +/- 0.52; 1.1 +/- .17, normal controls), histamine (mean 1.66 +/- .36; 0.62 +/- 0.08, normal controls), heparin (mean 1.61 +/- .38; 0.69 +/- .11, normal controls) occurred in peripheral blood mononuclear cells from all patients with rheumatoid arthritis compared with normal controls (P < .0236 to .0015) which was inhibited in 32% of peripheral blood mononuclear cells by anti-IL-4. Increased IL-4 ELISA levels in cultured supernatants were noted with heparin (P < .25) and collagen (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Increased interleukin-4 production in response to mast cell mediators and human type I collagen in patients with rheumatoid arthritis. 815 36

We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a new mAb (B18) specific for V gamma 8 of human TCR-gamma delta+ T cells. The B18+ population constituted a minor subset of the gamma delta T cells in peripheral blood (PB) of healthy persons (6 +/- 5%) and only 1 of 35 gamma delta T cell clones analyzed was positive. In contrast, the B18+ subset was a dominant gamma delta T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 +/- 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18+. Interestingly, a higher proportion of B18+ gamma delta T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 +/- 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18+ subset was more frequent among IL-2-expanded gamma delta T cells (42 +/- 20%) derived from synovial tissue than among IL-2-expanded cells derived from synovial fluid (p < 0.002) and PB from RA patients (p < 0.02) as well as normal PB (p < 0.002). The V-gene usage of 13 gamma delta T cell clones from the synovial fluid of arthritic patients was analyzed. All B18+ clones (n = 7) expressed mRNA for V gamma 8 together with mRNA for V delta 1 (n = 5) or mRNA for V delta 3 (n = 2). None of the B18- clones expressed V gamma 8 (n = 6). We conclude that the gamma delta T cell that expresses V gamma 8, together with mainly V delta 1, is a major gamma delta T cell subset among the IEL of the gut and a highly frequent subset in the synovial tissue of patients with RA. This subset may correspond to the mouse V gamma 7+ IEL, which has a high degree of amino acid sequence homology with the human V gamma 8 protein.
 ...
PMID:High expression of V gamma 8 is a shared feature of human gamma delta T cells in the epithelium of the gut and in the inflamed synovial tissue. 820 27

Topics include treatment of multiple sclerosis (MS) with T cell receptor (TCR) peptides, rheumatoid arthritis (RA) with IL-1ra, IL-2 toxin conjugate, or antibodies to TNF, to CD4, or to ICAM-1, sepsis and five other diseases with IL-1ra, and treatment of experimental animal diseases with soluble receptors, IL-12, TGF-beta2, or small molecule antagonists of cytokines.
 ...
PMID:Clinical and preclinical studies presented at the Keystone Symposium on Arthritis, Related Diseases, and Cytokines. 821 99

We have previously demonstrated that auranofin, at nanomolar concentrations, enhances T cell activation, as measured by IL-2 release and Tac expression. However, it is not clear how enhanced T cell activation might be related to therapeutic value, since rheumatoid arthritis is widely believed to be associated with overactivation of the immune response. In this study, we show that the action of auranofin on T cell activation is dramatically influenced by the glutathione levels of the responding cells. Under conditions of very low intracellular glutathione where the synthesis of glutathione is blocked, the action of auranofin is converted from enhancement to a profound inhibition of T cell activation. Since glutathione levels in rheumatoid arthritis are known to be abnormally low, these results may explain how auranofin can act to suppress the immunological processes leading to rheumatoid arthritis. In addition, this study further demonstrated the close link which exists between auranofin action and glutathione metabolism in lymphocytes.
 ...
PMID:The interaction of auranofin and buthionine sulfoximine blocks activation of human peripheral T lymphocytes. 824 58

The results of treatment of 54 cases of rheumatoid arthritis (RA) by warm needling (WN) and point-injection (PI) with Zhuifengsu are reported. Good clinical results were observed with an effective rate of 100%. At the same time, changes in cellular and humoral immunity and other parameters in peripheral blood were noted before and after treatment. The NK activity and IL-2 value in RA patients were found to be lower than those of normal individuals; both increased after treatment (P < 0.01). This suggests that the WN and PI with Zhuifengsu exert a regulatory effect on the cellular immunological function.
 ...
PMID:Effect of acupuncture and point-injection treatment on immunologic function in rheumatoid arthritis. 824 85

Cartilage degradation, a hallmark of rheumatoid arthritis, is attributed to serine and metalloproteases secreted by neutrophils, synovial lining cells, macrophages, and chondrocytes. A large proportion of synovial fluid lymphocytes contains the granule-associated serine proteases granzymes A and B. We report that lysates of IL-2-stimulated lymphocytes contain an enzymatic activity (ECMase; cartilage extracellular matrix 35S release assay; extracellular matrix degrading activity) that solubilizes matrix synthesized by chondrocyte monolayers. ECMase activity is inactivated by the serine protease inhibitor diisopropylfluorophosphate, is stored in dense granules and cleaves aggrecan proteoglycans but not free glycosaminoglycans, hyaluronic acid, or type II collagen. ECMase is mediated by a cationic protein with biochemical properties identical to granzyme B, inasmuch as it preferentially hydrolyzes the substrate Boc-Ala-Ala-Asp-SBzl, immunochemically cross-reacts with an antibody that binds to a conserved amino-terminal region of lymphoid-myeloid serine proteases, and has amino-terminal sequence identity with human Q31 granzyme B. Using an agarose gel electrophoresis technique to assess cleavage of the rat sarcoma aggrecan, the catalytic efficiency of granzyme B for the digestion of aggrecan (catalytic efficiency = 1.7 x 10(7) M-1 s-1) was 425-fold faster than the catalytic efficiency reported for human stromelysin-1 at pH 7.5 (catalytic efficiency 4000 M-1 s-1) and 3200-fold faster than granzyme A. Based on these observations, we propose that granzyme B, secreted from cytotoxic lymphocytes within the rheumatoid joint, may contribute to cartilage loss by degrading resident aggrecan.
 ...
PMID:Human granzyme B degrades aggrecan proteoglycan in matrix synthesized by chondrocytes. 825 16

AP-1 is a transcriptional activator composed of homo- and heterodimers of Jun and Fos proteins. It is involved in activation of genes, such as collagenase, stromelysin, IL-2 and TGF beta 1, by tumour promoters, growth factors and cytokines. AP-1 activity is also elevated in response to transforming oncogenes and is required for cell proliferation. AP-1 activity is subject to complex regulation both transcriptionally and post-transcriptionally. Transcriptional control of jun and fos gene expression determines the amount and composition of the AP-1 complex. The jun and fos genes are regulated both positively and negatively and are highly inducible in response to extracellular stimuli. Post translational control is also important. Both cJun and cFos are subject to regulated phosphorylation. In the case of cJun, phosphorylation of sites near the DNA-binding domain inhibits DNA-binding, while dephosphorylation reverses this inhibition. Phosphorylation of cJun on sites within the N-terminal activation domain increases its ability to activate transcription. The protein kinase phosphorylating these sites is stimulated by cytokines and growth factors. Another mechanism modulating AP-1 activity is transcriptional interference by members of the nuclear receptor family and is relevant for the pathophysiology of rheumatoid arthritis (RA). In RA, chronic inflammation leads to increased AP-1 activity in T cells,macrophages and synoviocytes as a response to secretion of cytokines such as IL-1 and TNF alpha. While the IL-2 gene plays a major role in T cell activation, another AP-1 target gene encodes an enzyme, collagenase, responsible for destruction of bone and tendon.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Various modes of gene regulation by nuclear receptors for steroid and thyroid hormones. 831 34

Soluble CD23 (sCD23) is increased by interleukin-4 (IL-4) and decreased by interferon-gamma (IFN-gamma). On the basis of cytokine profiles T-helper (Th) cells may be functionally divided into IL-2- and IFN-gamma-secreting Th1 cells, which are involved in cell-mediated immunity (CMI), and IL-4- and IL-5-producing Th2 cells, which are involved in humoral immunity. Compared with sex-matched controls (median 8.5) we found significantly elevated levels of serum sCD23 in patients with rheumatoid arthritis (median 22.7, P < 0.0002), with the highest levels detected in patients fulfilling an increasing number of the American Association revised criteria for rheumatoid arthritis. Soluble CD23 levels were also significantly raised in autoimmune thyroiditis (median 11.7, P < 0.02) and myasthenia gravis (median 10.4, P < 0.05). In contrast patients with either coeliac (median 6.5) or Crohn's disease (median 5.8) had reduced levels of sCD23 compared to appropriate controls (median 11.8), in both cases significant at P < 0.01. Variations in sCD23 may, therefore, reflect enhanced Th1 activity in the two later conditions in contrast to heightened Th2 activity within the three classical autoimmune conditions.
 ...
PMID:Variations in serum sCD23 in conditions with either enhanced humoral or cell-mediated immunity. 834 6


<< Previous 1 2 3 4 5 6 7 8 9 10