Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) promotes the growth of a variety of hematopoietic and nonhematopoietic cells, both benign and malignant. There is now evidence that osteoblast-like cells produce GM-CSF and their growth is stimulated by this cytokine in vitro. We have studied the effect of rhGM-CSF on DNA synthesis and cell proliferation in the human osteogenic sarcoma cell lines U-20S, G-292, MG-63, and HOS. RhGM-CSF stimulated a dose-dependent increase in radioactive thymidine incorporation in each of the four cell lines in the presence of serum-free media, and in two cell lines (HOS and U-20S) in the presence of fetal bovine serum (FBS). In addition, rhGM-CSF produced significant increases in cell proliferation in two cell lines (MG-63 and U-20S) in the presence of 2% FBS. These results suggest that GM-CSF may have an important role in the biology of human osteogenic sarcoma cells. The clinical implications of these findings merit further investigation.
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PMID:The effect of rhGM-CSF on the proliferation of osteogenic sarcoma cells. 206 68

Highly purified interleukin 1 (IL 1) obtained from stimulated human monocytes appeared to be growth inhibitory and cytocidal for a human melanoma cell line, A375. Although IL 1 did not have an immediate cytolytic effect, with time in culture the growth of the target cells was irreversibly inhibited. The cells eventually lysed and decreased markedly in number; the IL 1 effect can therefore be said to be cytocidal. IL 1 activity could not be separated from the cytocidal activity by a variety of chromatography procedures by using conventional and high-performance liquid chromatography (HPLC). The A375 melanoma cell line was also sensitive to another human cytokine alpha-lymphotoxin (alpha-LT) derived from a human B cell line. IL 1 also appeared to be partially growth inhibitory and cytocidal for a LT-sensitive mouse fibroblast cell line, L929; but not for LT-resistant cells, including a subline of L929; a human epithelial carcinoma cell line, HeLa; a human osteosarcoma cell line, HOS; and a mouse SV40-transformed kidney cell line, TU5. However, the LT-sensitive mouse fibroblast cell line, L-M, was resistant to IL 1. Therefore, the cytocidal activity of IL 1 only partially overlapped the target cell selectivity of alpha-LT. Although natural IFN-alpha and recombinant IFN-beta were appreciably growth inhibitory for the A375 cell line, natural and recombinant IFN-alpha and recombinant IFN-beta and IFN-gamma exhibited little cytocidal activity. Purified IL 1 did not have any antiviral activity, and conversely, IFN and alpha-LT were not co-mitogenic for thymocytes. Furthermore, by ELISA and radioimmunoassays, antibodies against human alpha-LT, tumor necrosis factor, and IFN-gamma did not react with IL 1, indicating that IL 1 is antigenically distinct from these other cytokines. These in vitro results suggest that IL 1 may play a role in host defense against some tumors as a cytocidal factor.
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PMID:Human interleukin 1 is a cytocidal factor for several tumor cell lines. 241 93

We have studied the internalization and subsequent nuclear localization of [125I]-rTNF-alpha in a human osteoblast-like cell line, HOS TE85. TNF-alpha is rapidly internalized and optimum cellular levels are achieved in approximately 20 minutes at 37 degrees C. A portion of the internalized cytokine is translocated to the nucleus as judged by its presence in highly purified nuclei as a 17-kDa form.
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PMID:Nuclear localization of tumor necrosis factor-alpha in human osteoblast-like cells. 802 90

Tumor necrosis factor-alpha (TNF-alpha), a 17-kDa cytokine produced by stimulated macrophages/monocytes, modulates the functions of a variety of cells and has been shown to induce bone resorption in vitro. However, the effects that TNF-alpha may have on the process of bone formation are not completely understood. In order to study the effects of TNF-alpha on matrix development and mineralization, we utilized a human osteoblastic cell line, HOS TE85. Our results show that HOS TE85, which has been shown to be responsive to hormones active on normal osteoblasts, forms an extensive extracellular matrix (ECM) that mineralizes during extended culture. Treatment during the development of the matrix with TNF-alpha has little effect on cell number and DNA synthesis, showing thereby that TNF-alpha is not cytotoxic to the cells. However, TNF-alpha inhibits the formation of alkaline phosphatase (AP)-positive foci in a dose-dependent manner at concentrations of 0.1-10 ng/ml. TNF-alpha treatment caused a significant decrease in the incorporation of collagen into the developing matrix. In addition, TNF-alpha treatment resulted in a significant decrease in the synthesis of AP by HOS TE85 cells during the process of ECM formation and resulted in a pronounced lack of mineralization of the ECM. These results indicate that TNF-alpha may be acting as an uncoupler by decreasing the synthesis and incorporation of proteins required for bone formation, and inhibiting matrix formation and mineralization in vitro.
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PMID:Formation and mineralization of extracellular matrix secreted by an immortal human osteoblastic cell line: modulation by tumor necrosis factor-alpha. 808 24

We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderately severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,XY with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies.
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PMID:Interstitial lung disease in an adult with Fanconi anemia: clues to the pathogenesis. 909 63

Oxidative stress has been frequently implicated in the initiation and promotion phases of carcinogenesis. Antioxidant enzymes, which can antagonize this process, are lowered in a number of malignancies even though different findings have been reported in the literature. It has been shown that tumors have less copper/zinc superoxide dismutase (Cu/Zn SOD) in comparison with the more metabolically active tissues, but there is a large overlap between normal and tumor tissue. In order to examine the relationship between osteosarcoma at different degrees of proliferation and differentiation and Cu/Zn SOD levels, four different human ostosarcoma cell lines: HOS, U-2 OS, MG63, Saos-2 were studied for their production and release of Cu/Zn SOD. A normal human stromal cell line was used as control. Osteosarcoma cells were stimulated with TNF alpha, a cytokine previously shown to have antiproliferative activity. The release of Cu/Zn SOD into the supernatant was higher for the HOS and U-2 OS lines when compared to the other cell lines evaluated both in basal condition and after incubation with TNF alpha. Elevated intracellular levels of Cu/Zn SOD were shown except for the HOS and U-2 OS which possess high concentrations of the enzyme at 24 hours declining during the other incubation periods. These concentrations were increased after TNF alpha treatment. The different behaviour of the four cell lines evaluated might be explained by their degree of differentiation.
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PMID:Copper/zinc superoxide dismutase expression by different human osteosarcoma cell lines. 961 84

We investigated the expression of different chemokines in the surnatants and inside the cells of four human osteosarcoma cell lines. HOS, U-2 OS, MG63 and Saos-2 cells were cultured for 24, 48, 72 hours both in basal conditions and after stimulus with TNF alpha. Human stromal cells were used as control. IL-8 and MCP-1 are present in higher concentration in the surnatants in contrast to RANTES which is present primarily inside the cells. IL-8 and MCP-1 are not totally expressed by all the human osteosarcoma cell lines in unstimulated conditions, but became detectable after TNF alpha treatment. In general, this cytokine stimulated the production and release of the three chemokines.
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PMID:Expression of different chemokines by human osteosarcoma cells in response to tumor necrosis factor-alpha. 1065 98

This study aimed at clarifying the role of Aminopeptidase N (APN), a Zn2+-dependent ectopeptidase localized on the cell surface of human osteosarcoma cell lines treated with proinflammatory cytokines. We investigated the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alpha) as well as the anti-inflammatory cytokine transforming growth factor beta (TGF-beta) for their influence on APN regulation. Soluble IL-6 receptor (sIL-6R) was always used together with IL-6 to achieve a stable effect. In addition, the invasive potential of the osteosarcoma cell lines MG63 and HOS was examined. Competitive RT-PCR and Ala-pNA activity assays revealed that IL-6 and sIL-6R significantly increased the mRNA expression and activity of APN in both osteosarcoma cell lines. Although IL-1beta significantly stimulated APN mRNA expression in both cell lines, it influenced the enzyme activity only in MG63. TNF-alpha and TGF-beta, however, had an effect neither on mRNA expression nor on the enzyme activity of APN in both cell lines. In the Matrigel invasion assay, IL-6 and sIL-6R significantly up-regulated the transmigration of these cell lines, whereas other cytokines did not. The up-regulated invasion was inhibited by bestatin, a specific inhibitor of APN. Cellular migration correlated highly with APN activity (r = 0.79, P < 0.002). These findings suggest that APN contributes to the invasive potential of human osteosarcomas enhanced by IL-6 and SIL-6R.
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PMID:Possible contribution of aminopeptidase N (APN/CD13) to invasive potential enhanced by interleukin-6 and soluble interleukin-6 receptor in human osteosarcoma cell lines. 1108 84

When monocytes were cocultured with human osteosarcoma-derived cells (HOS cells), multinucleated giant cell formation of monocytes was induced. Intriguingly, even when a filter was interposed between monocytes and HOS cells, polykaryocytes also appeared. The multinucleated giant cells have characters similar to osteoclast-like cells. These findings indicate that soluble factor(s) secreted from HOS cells play an important role in polykaryocyte formation from monocytes. Twelve cloned cells were established from HSOS-1 cells and their capacities of inducing osteoclasts were investigated. Three cloned cells inducing nos. 4 and 9 had an ability of inducing osteoclasts (multinucleated giant cells, TRAP, calcitonin receptor and c-src mRNAs, osteoresorbing activity), and three cells, including nos. 1 and 5, did not show the ability. HOS cells and the cloned cells expressed several cytokine mRNAs. M-CSF was detected in the culture fluids of HOS cells, which also expressed RANK and RANK/ODF/OPGL mRNAs. Intriguingly, HOS cells secreting a soluble osteoclast inducing factors(s) expressed TNF-alpha converting enzyme mRNA. Furthermore, OCIF/OPG inhibited HOS cell-induced osteoclastogenesis and soluble RANKL could be detected in the culture fluids of HOS cells expressing TACE, suggesting that one of soluble osteoclast-inducing factor(s) is soluble RANKL. When blood monocytes were indirectly cocultured with HSOS-1 cells or cloned no. 9 cells in the presence of OCIF for 14 days, HOS cell-mediated osteoclastogenesis was suppressed, indicating that RANK-RANKL system is involved in the HOS cell-mediated osteoclastogenesis.
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PMID:Human osteosarcoma-derived cell lines produce soluble factor(s) that induces differentiation of blood monocytes to osteoclast-like cells. 1178 67

We have recently demonstrated that a transcription factor, nuclear factor kappa B (NF-kappa B), plays a key role in the production of cytokine and cell adhesion molecules in osteoblastic cells. In the present study, we investigated the effects of vector-averaged gravity (clinostat rotation) on tumor necrosis factor (TNF)-alpha-induced activation of NF-kappa B in human osteoblastic HOS-TE85 cells. After a 72-hr clinostat culture, the cells were treated with TNF-alpha for 30 min. Electrophoretic mobility shift assay using the nuclear extracts revealed that the DNA-binding activity of NF-kappa B was substantially reduced in clinostat-cultured cells compared with the stationary control. Concomitantly, the transactivation of NF-kappa B was examined by a transfection study. The cells were transfected with a plasmid expressing a luciferase reporter gene driven by multimerized NF-kappa B sites. They were cultured in the clinostat for 48-hr, followed by a 4-hr treatment with TNF-alpha. Clinostat culture resulted in a significant decrease in the luciferase activities, being consistent with the decreased binding of NF-kappa B. These results indicate that exposure of HOS-TE85 cells to vector-averaged gravity impairs NF-kappa B activation by TNF-alpha.
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PMID:Effects of vector-averaged gravity on NF-kappa B activation in human osteoblast-like cells. 1222 76


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