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)

Schwann cells in culture divide in response to defined mitogens such as PDGF and glial growth factor (GGF), but proliferation is greatly enhanced if agents such as forskolin, which increases Schwann cell intracellular cAMP, are added at the same time as PDGF or GGF (Davis, J. B., and P. Stroobant. 1990. J. Cell Biol. 110:1353-1360). The effect of forskolin is probably due to an increase in numbers of PDGF receptors (Weinmaster, G., and G. Lemke. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:915-920. Neuropeptides and beta-adrenergic agonists have been reported to have no effect on potentiating the mitogenic response of either PDGF or GGF. We show that the neuropeptide calcitonin gene-related peptide (CGRP) increases Schwann cell cAMP levels, but the cells rapidly desensitize. We therefore stimulated the cells in pulsatile fashion to partly overcome the effects of desensitization and show that CGRP can synergize with PDGF to stimulate Schwann cell proliferation, and that CGRP is as effective as forskolin in the pulsatile regime. CGRP is a good substrate for the neutral endopeptidase 24.11. Schwann cells in vivo have this protease on their surface, so the action of CGRP could be terminated by this enzyme and desensitization prevented. We therefore suggest that CGRP may play an important role in stimulating Schwann cell proliferation by regulating the response of mitogenic factors such as PDGF.
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PMID:Calcitonin gene-related peptide promotes Schwann cell proliferation. 773 Apr 12

Using a cytofluorimetric assay, we found that immunocytes of the mollusc, Mytilus galloprovincialis, express CD10, a surface antigen known to be identical to neutral endopeptidase-24.11 (NEP). The spectrofluorimetric analysis demonstrates that the growth factors PDGF-AB and TGF-beta1 provoke an increase in NEP-like activity in membrane preparations from the immunocytes, but have no effect on the soluble form in the serum. On the other hand, computer-assisted microscopic image analysis reveals that NEP deactivates the PDGF-AB- and TGF-beta1-induced shape changes in immunocytes. However, Western blots show that, in solution, NEP does not cleave PDGF-AB or TGF-beta1, indicating that the inactivation is not due to proteolysis. These results suggest a functional interplay in invertebrate immunocytes between growth factors and NEP, as previously shown in vertebrate cells.
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PMID:Neutral endopeptidase-24.11 (NEP) deactivates PDGF- and TGF-beta-induced cell shape changes in invertebrate immunocytes. 1077 67

In chronic glomerulonephritis (GN) the development of the tissue damage and progression to fibrosis is related to the individual immune response which brings about excessive inflammation, failure to activate regression and glomerular repair and excessive fibrogenic activity. Therefore, the present standard treatment of GN has two aims, to fight the acute inflammation and to inhibit the progressive renal fibrosis. New avenues in the anti-inflammatory and immunosuppressive treatment of the active phase of glomerular diseases include the use of drugs proven to be of value in organ transplantation (mycophenolate mofetil, rapamycin or anti-immune adhesion and anti-co-stimulatory molecules). Interest has recently focused on anti-inflammatory cytokines (monoclonal antibodies, peptidic antagonists or anti-sense oligonucleotides against TNF-alpha, anti-PDGF-beta, anti-TGF-beta and cytokine receptor antagonists) and anti-inflammatory natural cytokines (such as IL4, IL10, IL13 or low doses of TGFbeta). Other drugs may act by depleting B cells (such as anti-CD20 monoclonal antibody) or on several immune pathways, such as thalidomide or anti-cyclooxygenase 2. Several anti-sclerogenic drugs are already used for treatment of the chronic phase of glomerular diseases, such as antagonists of angiotensin II, statins and antioxidants. Other drugs are still experimental, including endothelin receptor antagonists and neutral endopeptidase or vasopeptidase inhibitors and other drugs operating on extracellular matrix accumulation/degradation mechanisms, e.g., pirfenidone. There are extremely interesting developments concerning activators of endogenous anti-inflammatory mechanisms, such as those regulated by peroxisome proliferator activated receptors. There is a need for successful treatment of chronic GN in childhood. This short review of the most promising new drugs shows there is reason to believe that the next decade will provide exciting new tools for the treatment of these diseases in children.
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PMID:New perspectives in treatment of glomerulonephritis. 1467 33

The presence and the different functional aspects of cytokine-related molecules in invertebrates are described. Cytokine-like factors affect immune functions, such as cell motility, chemotaxis, phagocytosis and cytotoxicity. In particular, cell migration shows a species-specific effect for IL-1alpha and TNF-alpha and a dose-correlated effect for IL-8, PDGF-AB and TGF-beta1. Apart from some exceptions, the phagocytic effect increases significantly at all the concentrations tested and with all the species used. PDGF-AB, TGF-beta1 and IL-8 provoke conformational changes in mollusk immunocytes, involving the signaling transduction pathways of phosphatidylinositol and cAMP. PDGF-AB and TGF-beta1 partially inhibit the induced programmed cell death in an insect cell line, and the survival effect is mediated by the activation of phosphatidylinositol 3-kinase, PKA and PKC. The exogenous administration of these growth factors in an invertebrate wound repair model showed that they are able to control the wound environment and promote the repair process by accelerating the coordinated activities involved. Moreover, IL-1alpha, IL-2 and TNF-alpha are able to induce nitric oxide synthase. PDGF-AB and TGF-beta1 provoke an increase in neutral endopeptidase-24.11 (NEP)-like activity in membrane preparations from mollusk immunocytes, while NEP deactivates the PDGF-AB- and TGF-beta1-induced cell shape changes. Cytokines are also involved in invertebrate stress response in a manner extremely similar to that in vertebrates. Several studies suggest the existence on the mollusk immunocyte membrane of an ancestral receptor capable of binding both IL-2 and CRH. Furthermore, the competition found between CRH and a large number of cytokines supports the idea that invertebrate cytokine receptors show a certain degree of promiscuity. The multiple functions of cytokines detected in invertebrates underline another characteristic of mammalian cytokines, i.e. their great pleiotropicity. Altogether, the studies on the function of the invertebrate humoral factors show a close overlapping with those found in vertebrates, and the hypothesized missing correlation between invertebrate and vertebrate cytokine genes that is emerging from the limited molecular biology data present in literature might represent a very peculiar strategy followed by Nature in the evolution of cytokines.
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PMID:Invertebrate humoral factors: cytokines as mediators of cell survival. 1497 62