Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the key role of human homeobox (HOX) genes in development is well established, their function in adult cells is still under scrutiny. We have analyzed, in normal adult blood cell subpopulations, acute lymphoid leukemia (ALL) cells lines, and primary blasts, the RNA expression of all HOX-2 cluster genes (5'-2.5, 2.4, 2.3, 2.2, 2.1, 2.6, 2.7, 2.8, 2.9, 3') and nine genes in the HOX-1, -3, and -4 cluster by Northern blotting, RNAse protection, and/or reverse transcriptase polymerase chain reaction (RT-PCR). The analyzed HOX-1, -3, and -4 genes were never expressed in all tested cell populations. Natural killer (NK) cells activated in interleukin-2 (IL-2)/IL-1 beta-treated cultures exhibit a gradually increasing, abundant expression of three HOX-2 genes (2.2, 2.6, 2.8), while three other genes (2.3, 2.1, 2.7) are expressed at a lower level at late culture times. However, no HOX-2 gene is expressed in quiescent lymphocytes (NK, B and T [T-cell receptor (TCR) alpha/beta, gamma/delta lymphocytes, thymocytes] cells), granulocytes, and monocytes. In B- and T-ALL cell lines, HOX-2 genes are expressed according to different patterns: (1) widespread transcription (seven of nine genes, including 2.3 and 2.6) in the Peer line bearing the TCR gamma/delta; (2) expression of 2.5, 2.2, and 2.6 in the SEZ 627 line, which derives from an HTLV-1+ T-helper leukemia; (3) transcription of 2.3 and 2.6 in both the T-ALL CEM line and four B-ALL lines (interestingly, CALLA- B-ALL lines are constantly 2.3/2.6 RNA+); (4) no HOX-2 gene expression was detected in one T- and two B-ALL lines. Primary blasts from five T- and five pre-B-ALL showed selective expression of one or more HOX-2 genes, namely 2.5, 2.2, 2.6, and 2.7. Our data are compatible with the hypothesis that selected HOX-2 genes play a role in the IL-2/IL-1 beta-induced activation and/or proliferation of normal NK lymphocytes and possibly in the oncogenetic process of some T- and B-ALL.
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PMID:Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes. 135 62

We have previously shown that neutral endopeptidase (NEP; EC 3.4.24.11) regulates neuropeptide-induced responses. Recently, Pierart et al. reported that NEP degraded purified interleukin-1 (IL-1) using thymocyte proliferation assay. Since IL-1 is an important cytokine in the immune response and inflammation, we have assessed whether NEP hydrolyzes recombinant human IL-1 beta using three assay systems (bioassay, immunoassay, and HPLC analysis). NEP on the NALM-6 cells (both intact cells and the solubilized plasma membrane fraction) efficiently hydrolyzed Met5-enkephalin and substance P. However, NEP did not significantly decrease the amount of rhIL-1 beta assessed by the growth inhibitory activity of a human melanoma, by the immunoassay, or by the direct analysis on HPLC. Therefore, we conclude that NEP does not significantly hydrolyze rhIL-1 beta. Our results suggest that, in contrast to the regulatory role of NEP in neuropeptide-induced responses, NEP is not a regulatory enzyme for IL-1-induced responses.
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PMID:Neutral endopeptidase (EC 3.4.24.11) does not hydrolyze recombinant human interleukin-1 beta. 171 45

Human myeloma cells were purified from bone marrow aspirates from four patients having advanced myeloma, including one with common acute lymphoblastic leukemia antigen-positive myeloma. All of these myelomas had marked bone lytic lesions. From the culture supernatants of these purified myeloma cells, bone-resorbing activities were significantly revealed by 45Ca-release bone resorption assay, and IL-1 activities were also detected by IL-1 bioassay (mouse thymocyte comitogenic assay). Sandwich enzyme immunoassay for IL-1 alpha or IL-1 beta revealed that IL-1 beta was responsible for IL-1 activity of these culture supernatants. Furthermore, the bone resorbing activities of these culture supernatants were completely neutralized by pretreatment of anti-IL-1 beta, but not anti-IL-1 alpha antibody. By Northern blot analysis, IL-1 beta mRNA was identified from these myeloma cells. Therefore, it is concluded that myeloma cells produce IL-1 beta, which acts as bone-resorbing activity in multiple myeloma.
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PMID:Interleukin-1 beta rather than lymphotoxin as the major bone resorbing activity in human multiple myeloma. 278 13

Endopeptidase 24.11 (enkephalinase) is a membrane bound protease involved in the degradation of neuropeptides and hormones. Its presence on cells of the thymus and lymph nodes suggests a possible role in the inactivation of immune system mediators. IL-1 (both purified IL-1 beta and an IL-1-rich supernatant) bioactivity, as measured in the thymocyte proliferation assay, was found to disappear upon incubation with endopeptidase 24.11. This inactivation was dependent on both incubation time and enzyme concentration. IL-1 beta was protected by the presence in the incubation medium of phosphoramidon, a specific inhibitor of endopeptidase 24.11. After incubation of IL-1-rich supernatant with the enzyme, the thymocyte proliferation activity could be restored by adding purified IL-1 beta to the samples, indicating that neither the enzyme nor the buffer had any toxic effect on thymocyte proliferation. In the same experimental conditions, IL-2 activity was not destroyed by endopeptidase 24.11.
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PMID:Effect of human endopeptidase 24.11 ("enkephalinase") on IL-1-induced thymocyte proliferation activity. 325 97

Interleukin-1 beta (IL-1 beta) induces bronchial hyperresponsiveness (BHR) to bradykinin but not to acetylcholine. We examined whether this was mediated through the inhibition of neutral endopeptidase (NEP) activity and/or through the enhancement of airway microvascular leakage (AML) by IL-1 beta. We administered human recombinant IL-1 beta (500 U) or saline intratracheally and 24 h later measured the airway responses to bradykinin (1 mM; 45 breaths). IL-1 beta-treated rats showed a decrease of 18.5 and 21.1% of NEP activity in the lungs and tracheobronchial tree, respectively (P < 0.05), associated with an augmented response in total lung resistance to bradykinin but with no increase in Evans blue dye extravasation used as a marker of AML. Phosphoramidon (0.1 and 1 mM; 90 breaths), an NEP inhibitor, induced a dose-dependent increase in lung resistance to bradykinin without further enhancing BHR induced by IL-1 beta. Bradykinin-induced AML was not enhanced by phosphoramidon in either saline- or IL-1 beta-treated rats. Similarly, after captopril (1 mM; 90 breaths), an inhibitor of angiotensin-converting enzyme, there was no further enhancement of BHR to bradykinin induced by IL-1 beta. BHR to bradykinin induced by IL-1 beta may result from an inhibition of peptidase activity, such as NEP and angiotensin-converting enzyme, and is not associated with an enhancement of AML.
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PMID:Role of neutral endopeptidase in bronchial hyperresponsiveness to bradykinin induced by IL-1 beta. 777 37

Bone marrow (BM) stromal cells express CD10 (cALLA), a surface antigen now known to be a neutral endopeptidase (NEP-24.11). The function of CD10 in BM stroma is unknown, although purified NEP-24.11 is known to degrade different substrates including interleukin 1 beta (IL-1 beta). We have therefore employed a CD10-positive BM stromal cell line (L2AK) which proliferates in response to IL-1 beta to test the hypothesis that degradation of this cytokine is one of the functions of stromal CD10. We first showed that [3H]thymidine incorporation by L2AK cells is enhanced by IL-1 beta in a clear dose-dependent manner. Addition of the CD10 inhibitor, phosphoramidon, together with IL-1 beta resulted in a left shift in the dose-response curve which corresponded to a 10-fold potentiation of the IL-1 beta effect. These results indicate that CD10 on bone marrow stromal cells can degrade IL-1 beta and therefore provide a local control of the effects of this, and possibly other, growth factor(s).
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PMID:A function of CD10 on bone marrow stroma. 799 15

Tumour necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory agent produced primarily by activated monocytes and macrophages. TNF-alpha is synthesized as a precursor protein of M(r) 26,000 (26K) which is processed to a secreted 17K mature form by cleavage of an Ala-Val bond between residues 76-77. The enzyme(s) responsible for processing pro-TNF-alpha has yet to be identified. Here, we describe the capacity of a metalloproteinase inhibitor, GI 129471, to block TNF-alpha secretion both in vitro and in vivo. The inhibition is specific to TNF-alpha; the production of other secreted cytokines, such as the interleukins IL-1 beta, IL-2, or IL-6, is not inhibited. The mechanism of inhibition occurs at a post-translational step in TNF-alpha production. Our data suggest that TNF-alpha processing is mediated by a unique Zn2+ endopeptidase which is inhibited by GI 129471 and would represent a novel target for therapeutic intervention in TNF-alpha associated pathologies.
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PMID:Regulation of tumour necrosis factor-alpha processing by a metalloproteinase inhibitor. 805 11

To investigate the influence of interleukin-1 beta (IL-1 beta) on airway epithelial cell growth, we measured [3H]thymidine incorporation and cell numbers of cultured porcine tracheal epithelial cells in the presence or absence of human recombinant IL-1 beta with or without the following: goat antiporcine polyclonal antibody to platelet-derived growth factor (PDGF); IL-1 receptor antagonist; indomethacin; PD-145065, a combined endothelin-A and -B receptor antagonist; BQ-123, an antagonist selective for endothelin-A receptors; or phosphoramidon, an inhibitor, in part, of endothelin-converting enzymes, including neutral endopeptidase. We found that IL-1 beta stimulated the proliferation of airway epithelial cells, and this response was inhibited by the IL-1 receptor antagonist and by PD-145065 or BQ-123. However, neither indomethacin nor PDGF antibody was influential. The endothelin receptor antagonists also decreased basal thymidine incorporation by these cells as did phosphormidon, although to a lesser degree. Data from radioimmunoassays indicated that phosphormidon reduced the endogenous production of endothelin-1 from the cells, and IL-1 beta clearly increased it over time. We conclude that IL-1 beta is a stimulant of airway epithelial cell growth, and its mitogenic effects are mediated, in part, by endogenous endothelin-1 production.
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PMID:Interleukin-1 beta increases airway epithelial cell mitogenesis partly by stimulating endothelin-1 production. 904 68

Peptidases play an important role in the regulation of peptide-mediated effects. Modulation of peptidase activity may therefore be a major mechanism to control peptide actions. Our aim was to analyse the effects of cytokines and glucocorticoids on peptidases expressed by human bronchial epithelial cells, which have been shown to be an important site for peptidase activity. The effects of cytokines [interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), IL-4, interferon gamma (INF-gamma), and epidermal growth factor (EGF)] and/or dexamethasone (DEX) on both expression and activity of neutral endopeptidase (NEP) and aminopeptidase N (APN) by BEAS 2B cells were determined using flow cytometry and activity assays, respectively. IL-1 beta, and to a lesser extent, TNF-alpha and IL-4 increased NEP activity and expression, whereas IFN-gamma decreased NEP. The effect of IL-1 beta was mediated, at least in part, via a cAMP-dependent pathway which did not involve prostaglandin E2 synthesis. APN was increased after 24-h stimulation with IFN-gamma, whereas other stimuli had no effect. DEX strongly increased NEP and APN expression and activity, both in the absence and in the presence of cytokines. We conclude that cytokines and glucocorticoids are able to modulate the activity of NEP and APN on BEAS 2B cells. Our results suggest a role for the human bronchial epithelium in the control of inflammation and indicate that one beneficial effect of glucocorticoids on asthma may be upregulation of peptidases expressed by bronchial epithelial cells.
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PMID:Cytokines and glucocorticoids modulate human bronchial epithelial cell peptidases. 950 46