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

Gene transduction into immature human hematopoietic cells collected from umbilical cord blood, bone marrow, or mobilized peripheral blood cells could be useful for the treatment of genetic and acquired disorders of the hematopoietic system. Immunodeficient mouse models have been used frequently as recipients to assay the growth and differentiation of human hematopoietic stem/progenitor cells. Indeed, high levels of human cell engraftment were first reported in human/murine chimeras using NOD/SCID mice, which now are considered as the standard for these types of experiments. However, NOD/SCID mice have some clear disadvantages (including spontaneous tumor formation) that limit their general use. We have developed a new immunodeficient mouse model by combining recombinase activating gene-2 (RAG2) and common cytokine receptor gamma chain (gamma c) mutations. The RAG2-/-/gamma c- double mutant mice are completely alymphoid (T-, B-, NK-), show no spontaneous tumor formation, and exhibit normal hematopoietic parameters. Interestingly, human cord blood cell engraftment in RAG2-/-/gamma c- mice was greatly enhanced by the exogenous administration of human cytokines interleukin-(IL-3) granulocyte-macrophage colony-stimulating factor, (GM-CSF), and erythropoietin in contrast to the NOD/SCID model. This unique feature of the RAG2-/-/gamma c- mouse model should be particularly well suited for assessing the role of different cytokines in human lymphopoiesis and stem/progenitor cell function in vivo.
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PMID:A novel immunodeficient mouse model--RAG2 x common cytokine receptor gamma chain double mutants--requiring exogenous cytokine administration for human hematopoietic stem cell engraftment. 1038 66

The interleukin 4 (IL-4)/IL-4 receptor (IL-4R) system in promyelocytes is not well documented. Here, we used promyelocytic leukaemia PLB-985 cells differentiated with dimethylsulfoxide (PLB-985D) toward neutrophil-like phenotype to investigate the IL-4/IL-4R system. PLB-985 cells did not express CD132 (gammac) but expressed the complete IL-4 type II receptor (IL-4Ralpha and IL-13Ralpha1). Moreover, PLB-985 cells lost surface expression of IL-13Ralpha1 during differentiation, resulting in PLB-985D cells expressing only IL-4Ralpha fully responsive to IL-4, as judged by activation of mitogen-activated protein (MAP) kinases and Janus kinase 1. IL-4 also increased suppressor of cytokine signalling 3 (SOCS3) protein level in the presence of the proteasome inhibitor MG132 exclusively in PLB-985D cells. As the IL-4Ralpha chain has been associated with a component of the phagocyte NADPH oxidase, we used PLB-985-gp91(phox) deficient cells (mimicking chronic granulomatous disease, X-CGD), to investigate the IL-4/IL-4R system in X-CGD-D cells. IL-4 was found to activate MAP kinases in X-CGD-D cells but did not up-regulate SOCS3, in contrast to granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and IL-6. Utilization of catalase, cycloheximide and genistein inhibitors showed that IL-4 induced SOCS3 by a mechanism dependent on a complete NADPH oxidase complex, protein synthesis and tyrosine phosphorylation, but independent of production of reactive oxygen species. We conclude that IL-4 induces cell signalling in promyelocytes expressing only IL-4Ralpha.
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PMID:Investigation of the interleukin (IL)-4/IL-4 receptor system in promyelocytic leukaemia PLB-985 cells during differentiation toward neutrophil-like phenotype: mechanism involved in IL-4-induced SOCS3 protein expression. 1800 66