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)

Human osteoblast cultures derived as out-growths from trabecular bone released tumor necrosis factor (TNF alpha) upon stimulation of the cells with human recombinant interleukin 1 (IL1; 10(-13)-10(-11) M), human recombinant granulocyte-macrophage colony-stimulating factor (100-1000 U/ml), and bacterial lipopolysaccharide (5-500 ng/ml). The osteotropic hormones 1,25-dihydroxyvitamin D3, PTH, and calcitonin had no effect on TNF production. The TNF released by the osteoblasts was identified as TNF alpha, using a specific anti-TNF alpha monoclonal antibody to neutralize its activity. Immunohistochemical staining of the cells using the same antibody revealed that all of the cells in the cultures were capable of producing TNF alpha, including those that also expressed alkaline phosphatase activity. Immunoreactive protein could be detected in the perinuclear region when cells were cultured in the presence of monensin, suggesting accumulation of newly synthesised protein in the Golgi apparatus. These results suggest that human osteoblasts, which have been shown previously to respond to TNF alpha, can synthesize and release TNF in response to IL1 and granulocyte-macrophage colony-stimulating factor. TNF may, therefore, not only have a pathological role in conditions of chronic inflammation, but also may act as a local paracrine or autocrine regulator of osteoblast function.
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PMID:Production of tumor necrosis factor by human osteoblasts is modulated by other cytokines, but not by osteotropic hormones. 240 45

We demonstrated that 125I-labeled human parathyroid hormone (1-34;8,18-Nle,34-Tyr)[[125I]hPTH(1-34)] bound specifically to hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. Half-maximal inhibition of binding was achieved at concentrations of unlabeled hPTH(1-34) of about 5 x 10(-9)M. Insulin and hPTH(39-68) did not compete for PTH binding sites. Specific binding of hPTH(1-34) was detected in neither macrophages nor multinucleated cells (MNC's). Furthermore, treatment of hemopoietic blast cells with hPTH(1-34) stimulated MNC formation, and the range of concentrations (10(-10)-10(-8)M) over which hPTH(1-34) caused these effects was similar to that which inhibited the binding of [125I]hPTH(1-34). These findings suggest the presence of a PTH receptor on osteoclast precursors and the direct effect of PTH on them, resulting in osteoclast-mediated bone resorption.
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PMID:Existence of parathyroid hormone binding sites on murine hemopoietic blast cells. 255 Dec 92

The cellular mechanism by which PTH and other osteotropic substances stimulate bone resorption is unclear. One hypothesis is that PTH-stimulated osteoblasts release cytokines which activate osteoclasts or osteoclast precursors. To examine whether cytokines are released by osteoblast-like cells in vitro, medium conditioned by a clonal rat osteosarcoma cell line 17/2.8 (ROS) was examined for mitogenic activity using a helper T lymphocyte line HT-2. This line proliferates in response to interleukin-2 (IL-2), IL-4, and granulocyte-macrophage colony-stimulating factor (GM CSF). Conditioned medium (CM) from untreated ROS cells caused proliferation of HT-2 cells. Treatment of ROS cells with PTH or lipopolysaccharide (LPS) caused a dose-dependent increase in the secretion of this mitogenic activity. To further define the nature of this mitogenic activity, we examined the effect of incubation of CM with neutralizing antibodies to IL-2, IL-4, and GM CSF. Mitogenic activity induced by both PTH- and LPS-treated ROS cell CM was completely inhibited by anti-GM CSF antibody, whereas there was no reduction in activity in the presence of antibodies to IL-2 or IL-4. Partial purification of both PTH- and LPS-treated CM using reverse phase HPLC resulted in a single peak of HT-2 mitogenic activity, which in both cases was completely inhibited by anti-GM CSF antibody. These findings suggest that PTH- and LPS-treated ROS cells secrete a T cell mitogenic activity which, by functional, serological, and biochemical criteria, is indistinguishable from GM CSF.
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PMID:Osteoblast-like cells secrete granulocyte-macrophage colony-stimulating factor in response to parathyroid hormone and lipopolysaccharide. 264 12

Regulation of the production of the biologically active vitamin D3 sterol 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by cultured pulmonary alveolar macrophages (PAM) obtained from 6 patients with pulmonary sarcoidosis and from 9 normal subjects was studied. The sarcoid cells, all collected from patients with normal calcium metabolism, synthesized 1,25-(OH)2-[3H]D3 from the substrate 25-hydroxyvitamin [3H]D3 (25OH-[3H]D3), whereas in vitro incubation with recombinant human interferon-gamma (IFN gamma) or lipopolysaccharide (LPS) was required for induction of synthesis of the hormone by normal PAM. Exogenous 1,25-(OH)2D3 (10-100 nmol/L) decreased endogenous hormone production by normal PAM by approximately 45%. The relative inhibitory effect of 1,25-(OH)2D3 was less pronounced in sarcoid PAM, in which 10-100 nmol/L 1,25-(OH)2D3 inhibited 250HD3-1-hydroxylase by approximately 25%. An accompanying induction of the 250HD3-24-hydroxylase, which is typical for renal cells, was found at low levels in only 3 of 10 experiments; in this regard, no differences between sarcoid and normal PAM were apparent. PTH or forskolin did not influence 250HD3 metabolism by PAM. 1,25-(OH)2D3 production by sarcoid PAM was enhanced by lipopolysaccharide and IFN gamma. Likewise, recombinant human interleukin-2 stimulated 1,25-(OH)2D3 production by sarcoid PAM, suggesting a possible role for both IFN gamma and interleukin-2 in the induction of 1,25-(OH)2D3 synthesis by sarcoid PAM in vivo. Recombinant human IFN alpha, IFN beta, and granulocyte-macrophage colony-stimulating factor had little effect. Dexamethasone and chloroquine, which have in vivo antihypercalcemic activity in sarcoidosis, both inhibited 1,25-(OH)2D3 synthesis by sarcoid PAM; chloroquine simultaneously stimulated the 24-hydroxylase. Our studies suggest that the 250HD3-metabolizing system in PAM is in some respects different from renal metabolism of 250HD3.
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PMID:Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis. 311 53

The controversy still exists about the biological activity of carboxyl (C)-terminal PTH fragments. The present study was performed to examine the effect of C-terminal PTH fragments on osteoclast-like cell formation and bone-resorbing activity. In contrast to human (h) PTH-(1-34) or hPTH-(1-84), any C-terminal fragments examined [hPTH-(35-84), hPTH-(53-84), and hPTH-(69-84)] did not affect cellular cAMP production and intracellular calcium in osteoblastic UMR-106 cells. Although hPTH-(1-84) caused an increase in cAMP production and intracellular calcium less effectively than hPTH-(1-34) in UMR-106 cells, the former caused a stimulation of osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures more effectively than the latter. All of the C-terminal fragments significantly stimulated osteoclast-like cell formation, and their effectiveness seemed to depend on the amino acid length of the fragments. The conditioned medium from UMR-106 cells pretreated with C-terminal PTH as well as amino-terminal PTH significantly stimulated osteoclast-like cell formation from mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. Moreover, all of the C-terminal fragments stimulated osteoclast-like cell formation from hemopoietic blast cells even in the absence of osteoblasts, and their effectiveness seemed to depend on the length of fragments. As for bone-resorbing activity by mature osteoclasts, all of the C-terminal fragments stimulated bone resorption in osteoblast-containing mouse bone cell cultures, whereas these fragments did not affect the bone-resorbing activity of isolated rabbit osteoclasts. The present study first indicates that C-terminal PTH fragments stimulate osteoclast-like cell formation as well as bone-resorbing activity by mature osteoclasts in the presence of osteoblasts and accelerate osteoclast-like cell formation from hemopoietic blast cells in the absence of osteoblasts.
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PMID:Carboxyl-terminal parathyroid hormone fragments stimulate osteoclast-like cell formation and osteoclastic activity. 813 58