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)

Introduction of genes for cytokine receptors into hematopoietic stem/progenitor cells (HSC/HPC) may be of clinical use in the future. We recently reported that retroviral-mediated transduction of either the human erythropoietin receptor (hEpoR) or interleukin-9 receptor (hIL-9R) genes into highly purified HSC/HPC from cord blood (CB) resulted in increased numbers of detectable cytokine-responsive erythroid progenitors (burst-forming units-erythroid [BFU-E]). In the present study, we evaluated if this increase could be further enhanced by cotransducing both these genes into single isolated HSC/HPC. Single CD34++CD33-or low-expressing cells from CB were transduced with viral supernatant containing the hEpoR or hIL-9R genes or cotransduced with both genes. In the presence of Steel factor (SLF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), and IL-9, the numbers of erythroid colonies formed were significantly increased after transduction of cells with either the hIL-9R or hEpoR gene compared to mock-transduced cells. This increase was significantly enhanced in cells cotransduced with both genes compared with either gene alone. Integration and expression of both genes was confirmed by polymerase chain reaction (PCR) and reverse-transcriptase (RT)-PCR analysis, respectively. The data demonstrate that myeloid progenitors can be transduced at the single-cell level with both hEpoR and hIL-9R genes with resultant enhanced proliferation of these progenitors in the erythroid lineage by combinations of cytokines including Epo and IL-9.
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PMID:Influence of retroviral-mediated gene transduction of both the recombinant human erythropoietin receptor and interleukin-9 receptor genes into single CD34++CD33-or low cord blood cells on cytokine-stimulated erythroid colony formation. 864 64

It has been proposed that neutrophils are targets for interleukin-7 (IL-7) because this cytokine was found to increase the number of murine immature neutrophils in vivo. In addition, some nonhuman myeloid cell lines were shown to express the IL-7 receptor (IL-7R). Moreover, it was recently discovered that human neutrophils constitutively express the common gamma chain (gamma(c)), known to be a component of not only IL-7R, but also IL-2R, IL-4R, IL-9R, and IL-15R. Among these, we have recently observed that IL-4 and IL-15 are neutrophil agonists. All of the above observations prompted us to study IL-7-human neutrophil interactions. In this study, we investigated potential effects of IL-7 on a range of neutrophil responses. Although we were able to confirm the presence of the gamma(c) component on human neutrophils, we report, for the first time, that these cells lack the CDw127 component of IL-7R. When studying potential modulatory effects of IL-7 on human neutrophils, we found that IL-7 does not induce respiratory burst, phagocytosis, or cytoskeletal functions and does not alter gene expression. Positive controls were included in each assay and the expected results were obtained. In addition, in contrast to IL-4 and IL-15, we found that neutrophil apoptosis is not modulated by IL-7, while granulocyte-macrophage colony-stimulating factor, used here as control, strongly delayed this process as expected. We conclude that the sole expression of gamma(c) on human neutrophils is insufficient to modulate neutrophil responses with respect to the studied functions. Therefore, it cannot be proposed, based on studies performed with nonhuman cells or cell lines, that human neutrophils are targets for IL-7.
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PMID:Absence of the IL-7 receptor component CDw127 indicates that gamma(c) expression alone is insufficient for IL-7 to modulate human neutrophil responses. 917 15