Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is evidence that 2'-deoxycoformycin (DCF) functions as a differentiating agent. We examined the effects of DCF on the differentiation of HL-60 cells, a standard model of leukemic cell differentiation. DCF did not induce morphologic or histochemical evidence of differentiation, nor did it interact with retinoic acid, 1,25-dihydroxyvitamin D3, or interferon-gamma in inducing differentiation. Furthermore, DCF and agents that differentiated HL-60 cells had opposing effects on adenosine deaminase and 2',5'-oligoadenylate synthetase activity.
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PMID:Effects of 2'-deoxycoformycin on HL-60 cell differentiation, adenosine deaminase, and oligoadenylate synthetase. 231 12

Treatment of human amnion U cells with interferon increased the steady state level of mRNA encoding the double-stranded (ds) RNA-specific adenosine deaminase (AdD) as measured by Northern gel-blot analysis. A single major dsRNA-specific AdD transcript of approximately 6.7 kb was detected; the transcript was induced by both interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma). Likewise, Western immunoblot analysis revealed that a 150-kDa protein recognized by antiserum prepared against recombinant dsRNA-specific AdD was increased in the human amnion U and neuroblastoma SH-SY5Y cell lines treated with interferon. Both IFN-alpha and IFN-gamma induced the 150-kDa protein. These results, which establish that dsRNA-specific AdD is an IFN-inducible protein in human cells, have implications regarding the possible role of interferon in persistent viral infections.
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PMID:Mechanism of interferon action: double-stranded RNA-specific adenosine deaminase from human cells is inducible by alpha and gamma interferons. 761 88

It was previously shown that CD26 (DPP IV, EC 3.4.14.5) is a binding site for adenosine deaminase (ADA, EC 3.5.4.4) on T cells and that costimulation by some anti-CD26 monoclonal antibodies (mAbs) and anti-CD3 induces CD4+ T cell proliferation. The CD26 epitopes involved in costimulation, the precise sequence of the events preceding proliferation, and the response of CD8+ compared with CD4+ T cells to CD26 were not extensively studied. We therefore compared the effects of the novel TA5.9 anti-CD26 mAb, recognizing an ADA-binding epitope, and the clearly distinct anti-Ta1 reference anti-CD26 mAb for their costimulatory properties in various T cell subsets. Both purified CD4+ and CD8+ T cells proliferated upon costimulation with anti-CD3 and either anti-CD26 mAb, but anti-TA5.9 mAb induced a more potent response than anti-Ta1. Either anti-CD26 mAb, together with anti-CD3, caused a similar sequential up-regulation of CD69, CD25 (IL-2R alpha), and CD71 (transferrin receptor) expression on CD4+ and CD8+ T cells. The activation markers appeared faster on the CD45R0+ than on the CD45R0- subsets. After costimulation, CD4+ T cell cultures contained significant amounts of the Th1 cytokines IL-2, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). In CD8+ T cell cultures relatively more IFN-gamma and TNF-alpha but almost no IL-2 was measured after triggering of CD3 and CD26. Our data demonstrate that the recognition of the ADA-binding epitope is not a prerequisite for the costimulatory capacity of anti-CD26 mAbs. Both CD4+ and CD8+ T cells and their CD45R0- and CD45R0+ subsets are sensitive to various aspects of activation via CD26, but the magnitude and/or kinetics differ according to the anti-CD26 used and the T cell subset studied.
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PMID:Costimulation of CD4+ and CD8+ T cells through CD26: the ADA-binding epitope is not essential for complete signaling. 766 88

The effects of the carbocyclic nucleoside MDL 201,112 and the purine nucleoside adenosine on the interferon-gamma (IFN-gamma)-induced priming of macrophages (m phi s) for the respiratory burst and major histocompatibility class II (MHC class II) Ia+ antigen expression were compared. Priming of purified, peritoneal m phi s from Lewis (LEW/N) rats for 18 h with recombinant rat IFN-gamma (rRaIFN-gamma) in the presence of either adenosine (100 microM) or MDL 201,112 (10 microM) resulted in a fourfold decrease in superoxide anion (O2-) production after stimulation with opsonized zymosan. Both agents were effective even when added 2 or 4 h after rRaIFN-gamma treatment. Peritoneal m phi s from LEW/N rats stimulated with LPS/rRaIFN-gamma were observed to secrete immunoreactive and bioactive TNF-alpha over 18 h in vitro and this cytokine could be dose-dependently inhibited by MDL 201,112. MDL 201,112 did not bind to classical A1 or A2 receptors on rat brain homogenates. Physiological levels of adenosine deaminase, or treatment with the nucleoside transport inhibitor dipyridamole, reversed the effects of adenosine; however, these agents at physiological concentrations had little or no effect on the inhibition of O2- release mediated by MDL 201,112. Furthermore, incubation of LEW/N m phi s for 18 h in vitro with rRaIFN-gamma resulted in significant enhancement of MHC class II Ia+ antigen expression, and these levels could be blocked by nearly 50% by either MDL 201,112 (10 microM) or adenosine (100 microM). MDL 201,112 and adenosine were also effective in decreasing m phi opsonized zymosan-stimulated O2- levels and MHC class II Ia+ antigen expression in vivo. The effects of MDL 201,112 on the down-regulation of heat-killed M. tuberculosis-activated LEW/N m phi MHC class II Ia+ antigen expression in vitro appear to be mediated by a novel pathway, because there was no rank order of potency of ADO A1 or A2 agonist/antagonists (CCPA, NECA, XAC, or CPT) in our in vitro system. In summary, our data provide compelling evidence that immunoregulatory carbocyclic nucleoside analogues such as MDL 201,112 or adenosine appear to regulate LEW/N rat m phi activation through novel molecular mechanisms and may have important therapeutic implications for acute and chronic inflammatory diseases.
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PMID:Effect of the carbocyclic nucleoside analogue MDL 201,112 on inhibition of interferon-gamma-induced priming of Lewis (LEW/N) rat macrophages for enhanced respiratory burst and MHC class II Ia+ antigen expression. 807 90

The diagnosis of tuberculous ascites is often difficult because of the subtle clinical clues, poorly discriminative biochemical assays, delayed results of bacteriological studies and hazards of laparoscopy. Therefore, the role of ascites adenosine deaminase (ADA) activity and interferon-gamma (IFN-delta) level in distinguishing tuberculous from other causes of ascites was examined in 50 patients with ascites. Following bacteriologic culture, seventeen (34%) patients were found to have tuberculous ascites; nine (59.9%) of them had also schistosomal hepatic fibrosis (SHF). Therefore, 36% (9 out of 25) of all patients with SHF included in the study, had coexistent peritoneal tuberculosis despite the presence of transudative ascites and unrecognized clinical features. Ascites ADA activity was significantly higher in tuberculous than in other causes of ascites (P < 0.001) regardless of the presence of an underlying liver disease. A cut-off of 28 U/L reached a sensitivity of 94.4% and a specificity of 100%. A direct correlation was found between ascites ADA activity and total proteins in the tuberculous group (r = 0.613) and the only false-negative result occurred in a patient with SHF and low-ascites protein. Ascites IFN-delta level was also significantly higher in tuberculous ascites with or without SHF than in other causes of ascites (P < 0.05). A cut-off of 26 pg/ml reached a sensitivity of 81% and a specificity of 100%. There was no correlation between ascites ADA activity and IFN-delta level in the tuberculous group (r = 0.329). Based on the results of the present study, it can be concluded that tuberculous ascites should be considered as an important cause of ascites particularly in patients with underlying liver disease. Ascites ADA activity was more sensitive than ascites IFN-delta in diagnosing tuberculosis (TB). It has proved to be an easy, rapid, safe and reliable method for routine use in the early diagnosis of tuberculous ascites.
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PMID:The value of ascites adenosine deaminase activity and interferon gamma level in discriminating tuberculous from non-tuberculous ascites. 816 54

We measured the activity of adenosine deaminase (ADA) and the concentration of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the pleural effusions from 28 patients with tuberculosis, 30 with neoplastic diseases, 25 with bacterial infections and 18 with congestive heart failure or liver cirrhosis. The levels of ADA (83.0 +/- 32.1 IU/L) and IFN-gamma (795.0 +/- 666.4 pg/ml) in tuberculous effusions were significantly higher than those in other groups (p < 0.0001). IL-1 beta level in the effusions of bacterial infections (265.2 +/- 379.2 pg/ml) was higher than that in other groups (p < 0.0001). TNF-alpha level in the effusions of tuberculosis (31.7 +/- 36.7 pg/ml) and bacterial infections (69.5 +/- 232.9 pg/ml) was higher than that in other groups. IL-8 level of exudative effusions was higher than that of transudates. IL-2 was only present in 4 effusions from tuberculosis and 1 effusion from bacterial infections. Diagnostic utilities of cytokines and ADA for tuberculous effusion were evaluated using receiver operating characteristics (ROC) curve analysis. The cut-off points of ADA, IL-1 beta, IL-8, TNF-alpha and IFN-gamma determined in this analysis were 54 IU/L, 5.5 pg/ml, 405 pg/ml, 4.5 pg/ml and 28 pg/ml, respectively and the sensitivity and the specificity of them were 88.0% and 95.9%, 19.1% and 74.1%, 57.1% and 63.2%, 81.0% and 77.2%, and 96.2% and 98.5%, respectively. In ADA, TNF-alpha and IFN-gamma, the areas under the curve (AUC) that represent the diagnostic accuracy were 0.968, 0.719 and 0.993, respectively. AUC of IFN-gamma was significantly higher than that of ADA or TNF-alpha. In tuberculous pleural effusion, IFN-gamma was significantly correlated with TNF-alpha, IL-1 beta and ADA. The correlation was also present between TNF-alpha and ADA.
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PMID:[Clinical significance of cytokine measurement in pleural effusion]. 938 55

To determine whether interferon-gamma affects rat purine catabolic and salvage enzyme activities, rats were injected with interferon-gamma (600000 U/kg, i.p.) and, similarly to a vehicle-injected control group, killed before or after injection at 6, 12, and 24 h. Organ homogenates were prepared and enzymatic reactions with substrates were carried out, after which the products were measured either chromatographically or spectrophotometrically. Western and Northern blotting also were performed. In contrast to the vehicle-injected rats, interferon-gamma-injected rats showed a significant rise in xanthine oxidoreductase activity in the liver, while enzyme activity was unchanged in the spleen, kidney, and lung. Western analysis of hepatic xanthine oxidoreductase showed an increased concentration of this protein 12 and 24 h after interferon-gamma injection. Northern analysis disclosed an enhanced mRNA expression coding for this enzyme, peaking 12 h after injection. Contrastingly, the activities of adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine guanine phosphoribosyltransferase, and adenine phosphoribosyltransferase were not affected by interferon-gamma in any organ tested. While interferon-gamma causes an increased hepatic biosynthesis of xanthine oxidoreductase, the physiologic role of this enzyme induction remains undetermined.
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PMID:Effect of interferon-gamma on purine catabolic and salvage enzyme activities in rats. 1035 Jun 54

Adenosine, a purine nucleoside found at high levels in solid tumors, is able to suppress the recognition/adhesion and effector phases of killer lymphocyte-mediated tumor cell destruction. Here, we demonstrate that adenosine, at concentrations that are typically present in the extracellular fluid of solid tumors, exerts a profound inhibitory effect on the induction of mouse cytotoxic T cells, without substantially affecting T-cell viability. T-cell proliferation in response to mitogenic anti-CD3 antibody was impaired in the presence of 10 microM adenosine (plus coformycin to inhibit endogenous adenosine deaminase). Antigen-specific T-cell proliferation was similarly inhibited by adenosine. Anti-CD3-activated killer T (AK-T) cells induced in the presence of adenosine exhibited reduced major histocompatibility complex-unrestricted cytotoxicity against P815 mastocytoma cells in JAM and (51)Cr-release assays. Diminished tumoricidal activity correlated with reduced expression of mRNAs coding for granzyme B, perforin, Fas ligand and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), as well as with diminished Nalpha-CBZ-L-lysine thiobenzylester (BLT) esterase activity. Interleukin-2 and interferon-gamma synthesis by AK-T cells was also inhibited by adenosine. AK-T cells express mRNA coding for A(2A), A(2B) and A(3) receptors, but little or no mRNA coding for A(1) receptors. The inhibitory effect of adenosine on AK-T cell proliferation was blocked by an A(3) receptor antagonist (MRS1191) but not by an A(2) receptor antagonist (3,7-dimethyl-1-propargylxanthine [DMPX]). The A(3) receptor agonists (N(6)-2-(4-aminophenyl)ethyladenosine [APNEA] and N(6)-benzyl-5'-N-ethylcarboxamidoadenosine [N(6)-benzyl-NECA]) also inhibited AK-T cell proliferation. Adenosine, therefore, acts through an A(3) receptor to prevent AK-T cell induction. Tumor-associated adenosine may act through the same mechanism to impair the development of tumor-reactive T cells in cancer patients.
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PMID:Adenosine acts through an A3 receptor to prevent the induction of murine anti-CD3-activated killer T cells. 1199 7

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional modification of pre-mRNA catalysed by an RNA-specific adenosine deaminase (ADAR). A-to-I RNA editing has been previously reported in the pre-mRNAs of brain glutamate and serotonin receptors and in lung tissue during inflammation. Here we report that systemic inflammation markedly induces inosine-containing mRNA to approximately 5% of adenosine in total mRNA. Induction was the result of up-regulation of A-to-I RNA editing as both dsRNA editing activity and ADAR1 expression were increased in the spleen, thymus and peripheral lymphocytes from endotoxin-treated mice. Up-regulation of ADAR1 was confirmed in vitro in T lymphocytes and macrophages stimulated with a variety of inflammatory mediators including tumour necrosis factor-alpha and interferon-gamma. A late induction of RNA editing was detected in concanavalin A-activated splenocytes stimulated with interleukin-2 in vitro. Taken together, these data suggest that a large number of inosine-containing mRNAs are produced during acute inflammation via up-regulation of ADAR1-mediated RNA editing. These events may affect the inflammatory and immune response through modulation of protein production.
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PMID:Widespread inosine-containing mRNA in lymphocytes regulated by ADAR1 in response to inflammation. 1270 13

Tuberculous pleurisy as well as malignant pleuritis is a representative disease presenting pleural effusion. The diagnosis of tuberculous pleurisy is made from examination of pleural effusion, but the sensitivity of smear or culture of Mycobacterium tuberculosis from pleural fluid is generally low. Although the pleural fluid concentration of adenosine deaminase (ADA) is useful in terms of sensitivity or specificity, the value could be high in empyema or rheumatoid pleuritis. Thoracoscopic biopsy of pleura is more sensitive rather than conventional percutaneous needle biopsy, but is more invasive. Tuberculous pleural effusion is caused by delayed allergy which macrophage and T-helper 1 cells mainly relate and the stimuli of bacterial body consecutively induces T-helper 1 cytokines. Pleural fluid interferon-gamma (INF-gamma) is important not only in pathogenesis but also in diagnosis. We demonstrated that INF-gamma is a more sensitive and specific indicator for tuberculous pleurisy than ADA using receiver operating characteristics (ROC) analysis. Cytometric bead array (CBA) is a tool to simultaneously measure abundance of various cytokines and is expected to be a very useful method to provide informations for understanding a feedback mechanism of cytokine network. It is needed to clear the immunity in pleural fluid and to establish the less invasive and more useful method to diagnose tuberculous pleurisy.
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PMID:[Diagnosis and treatment of tuberculous pleurisy--with special reference to the significance of measurement of pleural fluid cytokines]. 1516 35


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