Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Freshly isolated peripheral blood mononuclear cells (PBMC) from 10 healthy volunteers, 28 patients with rheumatoid arthritis (RA), eight patients with osteoarthritis, and five patients with ankylosing spondylitis were examined for interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) production using monoclonal antibodies and an indirect immunofluorescent method. In freshly isolated PBMC from healthy controls very few cells were stained for either IL-1 type. All 20 RA patients who were not receiving parenteral gold therapy had PBMC staining for IL-1 alpha. In these patients, up to 7.5% of PBMC showed bright IL-1 alpha staining (range 1.2-7.5%). No IL-1 beta staining was seen. These IL-1 alpha-staining cells had a dendritic morphology and the percentage of cells staining correlated well with levels of C-reactive protein, an index of disease activity in these RA patients. Significantly fewer IL-1 alpha-staining cells were present in the peripheral blood of RA patients receiving gold therapy and in the blood of patients with osteoarthritis and ankylosing spondylitis. These IL-1 alpha-containing cells, circulating in the blood of RA patients and correlating with disease activity have not been previously described. These results support the idea that IL-1 alpha plays an important role in the pathogenesis of rheumatoid inflammation.
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PMID:Cells with dendritic morphology and bright interleukin-1 alpha staining circulate in the blood of patients with rheumatoid arthritis. 196 79

The AMLR (autologous mixed lymphocyte reaction) was performed in 24 control subjects, 41 patients with rheumatoid arthritis (RA), 19 patients with ankylosing spondylitis (AS), and 7 patients with psoriatic arthritis (PSA). It was found to be depressed in 21 of the RA subjects and this was linked to medication with sodium aurothiomalate or D-penicillamine. Addition of ultrapure interleukin 1 (IL-1), indomethacin, or catalase did not cause any improvement in the AMLR but some improvement was noted in those RA patients with subnormal AMLR when pure, recombinant interleukin 2 (IL-2) was added to the cultures. Since autoreactive T-cells are generated during the AMLR which are capable of providing help for immunoglobulin production, it is proposed that the defective AMLR seen after second-line drug treatment may be the mechanism whereby rheumatoid factor (RF) production is down-regulated during such treatment.
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PMID:Second-line drug treatment in rheumatoid arthritis associated with depressed autologous mixed lymphocyte reaction. 294 8

The activity of natural killer (NK) cells can be modified by a number of factors that either increase or suppress cytotoxicity. We have investigated in detail the cytokine induced killing of a NK resistant renal carcinoma cell line Cur by human NK cells. Preincubation of peripheral blood mononuclear cells with interferon alpha (IFN alpha), interleukin 2 (Il-2), interleukin 1 (Il-1) and tumor necrosis factor alpha greatly increased the rate and magnitude of Cur killing. Positively selected CD16 (+) cells were found to respond to cytokine stimulation and to mediate Cur killing. The effects of Il-2 and IFNa could be upregulated by costimulation of effector cells with Il-1 or TNF alpha. It was shown that TNF alpha induced Il-2 receptor expression on CD16(+) cells alone and even more in combination with Il-2. Studies of NK cell function in various rheumatic diseases revealed reduced NK cytotoxicity in peripheral blood and synovial fluid (SF), both in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). By contrast, normal NK function was found in patients with ankylosing spondylitis (AS) and psoriatic arthritis. A discordance with regard to the percentage of Leu 7 positive mononuclear cells and NK function in peripheral blood and SF was demonstrated. Minimal expression of Leu 7 positive cells and cytotoxicity was present in synovial membranes. NK function in rheumatic disease was largely independent of drug therapy. Natural killer (NK) cells are a subset of lymphocytes that mediate spontaneous cytotoxicity against certain tumor and virus infected cells without any known prior sensitation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of human natural killer cell function by cytokines and rheumatic disease. 307 75

We examined the spontaneous secretion of interleukin 1 (IL-1) from peripheral blood monocytes and staphylococcal protein A (SPA) induced secretion of interleukin 2 (IL-2) from peripheral blood mononuclear cells from 13 patients with active ankylosing spondylitis and 10 healthy controls. IL-1 and IL-2 secretion in the patient group was not measurably different from controls (p greater than 0.05). We also examined IL-1 and IL-2 generation in 7 patients before and 2 months after therapy with a nonsteroidal antiinflammatory agent, piroxicam. A variable effect of piroxicam was observed on IL-1 and IL-2 generation despite the efficacy of piroxicam in reducing the clinical activity of the disease. Our results suggest the absence of an intrinsic aberration in IL generation from peripheral blood cells from patients with ankylosing spondylitis.
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PMID:Interleukin 1 and interleukin 2 generation by peripheral blood cells from patients with ankylosing spondylitis. 349 47

Synovial fluids from patients with rheumatoid arthritis (13 cases), ankylosing spondylitis (six), psoriatic arthritis (two), osteoarthritis (three) and rubella arthritis (four) contain interleukin-1 (Il-1) activity as measured in the CH3/He mouse thymocyte assay. That this activity is Il-1 was shown by: (i) the time course of thymocyte stimulation; (ii) failure of PHA blast cells to absorb out the activity; (iii) molecular weight of 15,000-20,000 daltons, and (iv) ability to stimulate prostaglandin E2 production from synovial cells. These results indicate that IL-1 is an important mediator in the inflammatory pathway of different types of joint disease.
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PMID:Cytokines and the chronic inflammation of rheumatic disease. I. The presence of interleukin-1 in synovial fluids. 660 91

The aim of this article is to critically review the potential role of aceclofenac in the treatment of inflammatory pain and chronic osteoarticular disorder, based on its activity on the mediators of inflammation, its effect on cartilage remodeling and on the results of clinical studies comparing aceclofenac with other NSAIDs in these disorders. Aceclofenac has an outstanding anti-inflammatory profile, involving besides a classical inhibition of prostaglandins E2, a decrease in the expression of several cytokines including interleukin 1 and tumor necrosis factor alpha. It also inhibits activated oxygen species production and influences cells adhesion. Aceclofenac and its main metabolite, 4-hydroxyaceclofenac, has positive effects on cartilage anabolism combined with modulating effect of matrix catabolism. Clinically, aceclofenac has been consistently shown to have a similar efficacy than that of widely marketed NSAIDs and a tolerance profile at least as good, if not better than the profile observed for other NSAIDs in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. As of today, no head to head comparison between aceclofenac and coxibs have been performed, nor for efficacy neither for tolerance. The specific profile of aceclofenac makes this NSAID an interesting candidate for long-term treatment of chronic rheumatic disorders as well as for treatment of acute inflammatory episodes.
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PMID:[What is the role of aceclofenac in the therapeutic arsenal against chronic osteoarthritis pathologies?]. 1152 98

Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom replaces the central atom of oxygen. They are indicated in non-neoplastic diseases including osteoporosis, corticosteroid-induced bone loss, Paget disease, and in cancer-related diseases such as neoplastic hypercalcemia, multiple myeloma and bone metastases secondary to breast and prostate cancer. There is now extensive in vitro evidence suggesting a direct antitumor effect of bisphosphonates at different levels of action. Some new in vitro and in vivo studies support the cytostatic effects of bisphosphonates on tumor cells, and the effects on the regulation of cell growth, apoptosis, angiogenesis, cell adhesion, and invasion, with particular attention to biological properties. Well designed clinical trials are necessary to investigate whether the antitumor potential of bisphosphonates may be clinically relevant. On the basis of their effects on macrophages, we may divide bisphosphonates into two distinct categories: aminobisphosphonates, which sensitize macrophages to an inflammatory stimulus inducing an acute-phase response, and non-aminobisphosphonates that can be metabolized into macrophages and that may inhibit the inflammatory response of macrophages. There is evidence of aminobisphosphonate-induced pro-inflammatory response, in particular, related to modifications of the cytokine network. Several in vivo studies have demonstrated an acute-phase reaction after the first administration of aminobisphosphonates, with a significant increase in the main pro-inflammatory cytokines. However, a peculiar aspect concerning the action of non-aminobisphosphonates seems to be an anti-inflammatory activity caused by the inhibition of the release of inflammatory mediators from activated macrophages, such as interleukin (IL)-6, tumor necrosis factor-alpha and IL-1. The inhibition of inflammatory responses is demonstrated in both in vivo and in vitro models. This activity suggests the use of non-aminobisphosphonates in several inflammatory diseases characterized by macrophage-mediated production of acute-phase cytokines, as prevention of erosions in rheumatoid arthritis, and of loosening of joint prostheses, as well as possibly in osteoarthritis, ankylosing spondylitis, myelofibrosis, and hypertrophic pulmonary osteoarthropathy.
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PMID:Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. 1524 2

Monocytes/macrophages play an important role in rheumatoid arthritis (RA) pathogenesis. They can activate fibroblasts through many molecules, including IL-1 and tumor necrosis factor-alpha, but there have been very few reports on the role of CD147 in RA. In our study, the results of flow cytometry reveal that the mean fluorescence intensity (MFI) of CD147 expression on CD14+ monocytes of peripheral blood from RA patients was higher than that in normal control and ankylosing spondylitis (AS) patients. The MFI of CD147 expression on the CD14+ monocytes in RA synovial fluid was higher than that in RA peripheral blood. Immunohistochemical staining shows that CD147 expression in RA synovium correlated with matrix metalloproteinase (MMP)-1 expression. A double immunofluorescent assay shows that CD147 was expressed on CD68+ cells in RA synovium. The potential role of CD147 in cyclophilin A (CyPA)-mediated cell migration was studied using a chemotaxis assay in vitro and it was found that the addition of anti-CD147 antibody or a CD147 antagonistic peptide significantly decreased the chemotactic index of the mononuclear cells. The role of CD147 in MMP production and cell invasion in vitro were studied through the co-culture of human CD14+ monocytes or monocytic line THP-1 cells and human fibroblasts, as well as by gel zymography and an invasion assay. Significantly elevated release and activation of MMP-9 and/or MMP-2 were seen in the co-culture of human monocytes/THP-1 cells and fibroblasts compared with cultures of the cells alone. An increased number of cells invading through the filters in the invasion assays was also observed in the co-cultured cells. The addition of CD147 antagonistic peptide had some inhibitory effect, not only on MMP production but also on cell invasion in the co-culture. Our study demonstrates that the increased expression of CD147 on monocytes/macrophages in RA may be responsible for elevated MMP secretion, cell invasion and CyPA-mediated cell migration into the joints, all of which may contribute to the cartilage and bone destruction of RA. These findings, together with a better understanding of CD147, CyPA and RA, will help in the development of innovative therapeutic interventions for RA.
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PMID:Expression of CD147 on monocytes/macrophages in rheumatoid arthritis: its potential role in monocyte accumulation and matrix metalloproteinase production. 1620 18

TNF-alpha neutralising agents such as Infliximab (Remicade), Etanercept (Enbrel) and the IL-1 receptor antagonist Anakinra (Kineret), are currently used clinically for the treatment of many inflammatory diseases such as Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriatic arthritis and psoriasis. These protein preparations are expensive to manufacture and administer, need to be injected and can cause allergic reactions. An alternative approach to lowering the levels of TNF-alpha and IL-1beta in inflammatory disease, is to inhibit the enzymes that generate these cytokines using cheaper small molecules. This paper is a broad overview of the progress that has been achieved so far, with respect to small molecule inhibitor design and pharmacological studies (in animals and humans), for the metalloprotease Tumour Necrosis Factor-alpha Converting Enzyme (TACE) and the cysteine protease Caspase-1 (Interleukin-1beta Converting Enzyme, ICE). Inhibitors of these two enzymes are currently considered to be good therapeutic targets that have the potential to provide relatively inexpensive and orally bioavailable anti-inflammatory agents in the future.
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PMID:Inhibitors of TACE and Caspase-1 as anti-inflammatory drugs. 1637 99

The spondyloarthropathies constitute a group of inflammatory joint diseases linked by shared characteristics that include a strong common genetic background. Genetic factors include major histocompatibility complex (MHC) genes, among which HLA-B27 contributes 30% of the overall genetic susceptibility to spondyloarthropathies, and non-MHC genes, none of which have been identified to date. Genome screens have identified regions that may contain susceptibility genes for spondyloarthropathies. In particular, a locus on the long arm of chromosome 9 (9q31-34) was identified by two groups working independently from each other. Studies using the candidate gene approach ruled out a role for most of the tested genes, including CARD15/NOD2. However, several independent groups have reported significant associations between ankylosing spondylitis and the IL-1 gene cluster on the long arm of chromosome 2.
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PMID:The genetics of spondyloarthropathies. 1665 Jul 94


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