Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminopeptidase N (APN) and dipeptidylpeptidase IV (DPIV) are transmembrane type II molecules widely distributed in mammalian tissues. In recent years, the interest in cell surface peptidases has increased considerably because, among other things, several reports indicate roles of ectopeptidases in tumour cell metastasis. Investigations into the regulation of APN and DPIV on tumour cells are rare. We report, for the first time, that IL-4 and IL-13 can up-regulate protein expression as well as enzymatic activity of both the peptidases on renal carcinoma cells and renal tubular epithelial cells in culture. The analysis of mRNA by competitive polymerase chain reaction (PCR) confirmed our results with respect to the APN increase at the level of gene expression. IL-1 beta and tumour necrosis factor-alpha (TNF-alpha) augmented the IL-4-induced effect with respect to APN but not to DPIV. A 5-day incubation with interferon-gamma (IFN-gamma) increased protein expression, especially of APN and, to a lesser extent, also of DPIV, whereas no significant increase in enzymatic activity could be observed. Small concentrations of transforming growth factor-beta 1 (TGF-beta 1) inhibit the expression and enzyme activity of DPIV. IL-6, IL-7, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been found to be without any effect on APN and DPIV. For a prospective therapeutic regimen with T cell-derived cytokines it has to be considered that--besides their effect on tumour cell growth--cytokines might affect surface ectopeptidases involved in tumour cell adhesion processes. The inhibition of APN and DPIV could be a new approach to suppression of cancer spread.
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PMID:Stimulation of the expression and the enzyme activity of aminopeptidase N/CD13 and dipeptidylpeptidase IV/CD26 on human renal cell carcinoma cells and renal tubular epithelial cells by T cell-derived cytokines, such as IL-4 and IL-13. 774 67

Aminopeptidase N (CD13) is a cell surface metalloprotease involved in growth regulation, tumor invasion, and down-regulation of regulatory peptides. CD13 expression on eosinophils in bronchoalveolar lavage (BAL) of asthmatics 10 minutes and 18 hours after segmental allergen provocation was significantly increased (+225% to +294%) compared to blood eosinophils. In vitro CD13 expression could be induced on blood eosinophils by transendothelial migration of the cells across interlenkin (IL) 1beta-activated human umbilical cord vein endothelial cells (HUVECs) as well as by the exposure to the cytokines IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). The cytokines GM-CSF and IL-5 were significantly less effective in inducing CD13 compared to IL-3. The IL-3-induced expression of CD13 was decreased in the presence of the protein-synthesis inhibitor cycloheximide (-8.8%). Moreover, blocking of CD13 by the protease inhibitors actinonin and bestatin significantly enhanced migration (+40.0% to +80.0%) of eosinophils across HUVEC monolayers. In summary, the data suggest that CD13 is regulated both by the process of transmigration and by the cytokine IL-3. Further, CD13 itself seems to be involved in the process of eosinophil transmigration. aminopeptidase Nendothelial cellseosinophilsinterleukin-3interleukin-5transendothelial migration
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PMID:Differential regulation of aminopeptidase N (CD13) by transendothelial migration and cytokines on human eosinophils. 1255 54