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)

In studies of the regulation of hematopoiesis, increasing attention has focused on the role of bone marrow stromal cells as rich sources of various cytokines. Present studies indicate that marrow stromal cells and monocytes produce activin A, implicating this new cytokine in the paracrine control of hematopoiesis. Activin A, which was initially recognized as a beta A beta A dimeric gonadal protein, was found to potentiate the proliferation and differentiation of erythroid progenitors; both purified erythroid colony-forming units (CFU-E) and K562 cells possess high affinity receptors specific for activin A. Present studies using Western and Northern blots demonstrate the presence of beta A subunits of activin A in the conditioned medium of monocytes and stromal cells and its RNA transcripts in these cells. The presence of functional and homodimeric beta A beta A activin molecule was confirmed through bioassay with or without a blocking antiserum against activin A or an activin binding protein, follistatin; its presence is further supported by a specific enzyme-linked immunosorbent assay (ELISA) in which a monoclonal antibody reacted only with the beta A beta A dimeric form of this molecule. In other experiments, the production of activin A was found to be regulated by various cytokines and regulators. The production of activin A in monocytes was stimulated more than ninefold by treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF). Activin A expression was also stimulated, albeit less potently, by bacterial lipopolysaccharide (LPS) and gamma-interferon. On the other hand, the expression of activin A in marrow stromal cells was upregulated by incubation with tumor necrosis factor-alpha (TNF-alpha), LPS, and interleukin 1 alpha (IL-1 alpha). Therefore, we propose that the local production of activin A in the microenvironment within bone marrow may fine tune the regulation of steady-state hematopoiesis. In addition, this factor may normally be produced at minimal levels, but under certain situations may be further induced to provide important biological functions.
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PMID:Regulation of production of activin A in human marrow stromal cells and monocytes. 142 3

A factor with burst-promoting activity (BPA) stimulates the formation of erythroid bursts in the presence of erythropoietin, acting on early erythroid progenitor cells (erythroid burst-forming units, or BFU-E). Here we investigated the biological properties of this factor partially purified from the urine of anemic patients. The human urinary factor did not cause the formation of late erythroid progenitor cells (erythroid colony-forming units, or CFU-E) or enhance such colony formation in the presence of erythropoietin. Thus, the urinary factor was a different substance from erythroid potentiating activity and from activin, which act on both BFU-E and CFU-E. The urinary factor promoted the colony formation of BFU-E from both humans and mice, but the human hematopoietic growth factors such as recombinant interleukin-3, interleukin-6, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor did not stimulate the formation of BFU-E derived colonies from mice. The results suggested that the factor in the urine of anemic patients was different from the hematopoietic growth factors identified so far.
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PMID:Factor with erythroid burst-promoting activity in human urine unlike other hematopoietic growth factors. 175 47

Activin and inhibin are biomolecules that, respectively, enhance and suppress the release of follicle-stimulating hormone from pituitary cells in vitro. Purified recombinant human (rhu) activin A and inhibin A were assessed for their effects on colony formation in vitro by human multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells. It was found that (i) rhu-activin A enhances colony formation by normal bone marrow erythroid and multipotential progenitor cells; (ii) purified rhu-inhibin A decreases activin, but not rhu-interleukin 3, rhu-granulocyte-macrophage colony-stimulating factor, or rhu-interleukin 4, enhancement of erythropoietin-stimulated colony formation by erythroid and multipotential progenitor cells; (iii) modulatory actions of rhu-activin and rhu-inhibin are mediated through monocytes and T lymphocytes within the marrow; (iv) actions are apparent in the absence or presence of serum; and (v) rhu-activin and rhu-inhibin have no effect on colony formation by granulocyte-macrophage progenitor cells. This defines an indirect mode of action and a specificity for activin and inhibin on multipotential and erythroid progenitor cells.
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PMID:Selective and indirect modulation of human multipotential and erythroid hematopoietic progenitor cell proliferation by recombinant human activin and inhibin. 319 7