Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We established a human bone marrow stromal cell line (Saka) by infecting marrow adherent cells from semisolid marrow cultures with a recombinant simian virus-40 (SV40) virus. The cells expressed SV40 large tumor antigen, had a fibroblast-like shape, and expressed fibronectin and vimentin. They did not contain detectable alkaline phosphatase activity; express myeloid, lymphoid, or factor VIII-associated antigens; or develop adipocyte-like characteristics with dexamethasone treatment. Polymerase chain reaction analysis of Saka cell RNA detected expression of messenger RNAs for interleukin-6 (IL-6), IL-1 beta, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, and the 1,25-dihydroxyvitamin D3 receptor. Coculture of Saka cells with human marrow mononuclear cells enhanced formation of osteoclast-like multinucleated cells (MNC) in long term human bone marrow cultures. These MNC expressed calcitonin receptors and formed resorption lacunae on dentine. In contrast, coculture of marrow mononuclear cells with other SV40-transformed human marrow stromal cell lines did not increase MNC formation. Conditioned medium from Saka cells or coculture of bone marrow and Saka cells separated by a Millipore membrane did not enhance MNC formation. Addition of a neutralizing antibody to IL-6 or IL-1 beta blocked the effects of Saka cells on MNC formation. These results suggest that marrow stromal cells enhance osteoclast formation in part through direct cell to cell contact and production of IL-6 and/or IL-1 beta.
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PMID:Development and characterization of a human marrow stromal cell line that enhances osteoclast-like cell formation. 753 99

Tumor necrosis factor-alpha (TNF-alpha), a cytokine produced by astrocytes in vivo and in vitro, was tested for its effects on two malignant astrocytoma cell lines (A-172, U-87). Both lines were immunoreactive for glial fibrillary acidic protein, vimentin, Class I antigens, and interleukin-6. The lines differed in their expression of Class II and intercellular adhesion molecule-1 (ICAM-1) antigenic determinants: A-172 cells were negative for both Class II and ICAM-1 antigens, while U-87 cells were intensely positive for Class II and weakly positive for ICAM-1. When these astrocytoma cell lines were exposed to TNF-alpha, A-172 growth was stimulated while U-87 growth was inhibited. Furthermore, in U-87 cells, TNF-alpha enhanced both ICAM-1 and interleukin-1 beta (IL-1 beta) expression, and decreased immunoreactivity for transforming growth factor-beta (TGF-beta) protein. In contrast, in the presence of TNF-alpha, A-172 cells remained negative for IL-1 beta and TGF-beta, but showed an increased expression of ICAM-1. These results demonstrate that TNF-alpha can induce changes in growth rate, cytokine production, and surface antigen expression in malignant astrocytomas; however, the nature of these changes is dependent on the specific characteristics of these malignant astrocytomas. The resultant variability in the immunological microenvironment of these tumors may reflect differences in their growth potential.
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PMID:Differential effects of tumor necrosis factor-alpha on proliferation, cell surface antigen expression, and cytokine interactions in malignant gliomas. 809 40

Interleukin-6 (IL-6) is a pleiotropic mediator of immune function and a growth factor for a variety of hematopoietic cell types. Because IL-1 beta is known to induce IL-6 production in nonplacental mesenchymal cells and is locally produced by maternal decidua, this study was designed to determine whether IL-1 beta could regulate IL-6 production by second trimester placental villous core mesenchymal cells (VCMC) in vitro. VCMC were prepared for culture by enzymatic digestion of placentas (14-20 weeks gestation; n = 7). Immunohistochemistry performed on the confluent cells demonstrated that more than 95% of the cells had a fibroblast-like morphology and were vimentin positive, less than 5% were leukocyte common antigen (CA-45) positive, and no trophoblast contamination was demonstrated by the lack of cytokeratin staining. In dose-response experiments, a specific dose-response induction of IL-6 mRNA expression and IL-6-immunoreactive protein production by IL-1 beta was demonstrated; this was first seen at 100 pg/ml IL-1 beta [455 +/- 191 ng/ml (+/- SEM); controls, 42 +/- 16 ng/ml; P < 0.05]. In time-course studies, the addition of 10 ng/ml IL-1 beta significantly increased IL-6 production rates; this was first seen at 8 h of culture and increased in a linear fashion up to 48 h. At 48 h of culture, IL-6 levels were 17 times higher in treated VCMC (861 +/- 179 ng/ml) compared to those in nontreated VCMC (51 +/- 14 ng/ml). In summary, IL-1 beta stimulates VCMC IL-6 production in a specific dose- and time-dependent manner. From these results, we conclude that VCMC are an important source of IL-6 in second trimester placenta and that production of placental IL-6 be may regulated by decidual IL-1 beta.
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PMID:Interleukin-1 beta stimulates interleukin-6 production in placental villous core mesenchymal cells. 827 59

A mesothelioma cell line, termed T-85, was established from a patient with malignant peritoneal mesothelioma and remarkable thrombocytosis (1.4 x 10(6)/mm3). Electron microscopically, two types of mesothelioma cells have been characterized; the major type of cells with dense-cored granules in the cytoplasm and the minor one with evenly dense granules. Immunologically, the cells showed staining for interleukin-6 (IL-6), cytokeratin, collagen type IV, vimentin, laminin, fibronectin and Factor VIII-related antigen. Quantitation by ELISA revealed a high concentration of IL-6 in T-85 cell culture supernatants. RT-polymerase chain reaction of T-85 cells showed two positive bands of cDNA at 628 and 251 base pairs indicating the constitutive expression of IL-6 and IL-6 receptor mRNA. Moreover, prominent pro-platelet process formation activity in T-85 cell culture supernatants indicated the presence of a thrombopoietic activity due mainly to IL-6 but not the c-Mpl ligand or erythropoietin. However, the fact that 15% of PPF activity remained in the supernatants treated with anti-IL-6 antibody indicated the presence of another thrombopoietic substance. T-85 is so far the first mesothelioma cell line derived from a case with remarkable thrombocytosis.
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PMID:Establishment and characterization of a new human mesothelioma cell line (T-85) from malignant peritoneal mesothelioma with remarkable thrombocytosis. 887 1

Sclerosing pseudotumorous immune reactions of the retroperitoneum have been shown to consist of HLA-DR-positive spindle-shaped fibroblasts and macrophages that resemble fibroblasts, and in some instances they contain clonal populations of T lymphocytes not found in granulation tissue, keloids, nodular fasciitis, or fibromatoses. In patients who are iatrogenically immunosuppressed, circulating monocytes may be induced in vitro to transform into spindle-shaped macrophages, and secrete collagen after stimulation by conditioning medium from activated T lymphocytes. The authors investigated a series of five inflammatory pseudotumors (IPT) of lymph node origin for identification of spindle-shaped macrophages, T-cell receptor gene rearrangements, and lymphocyte-derived cytokine mRNA production. All cases of IPT demonstrated spindle-shaped macrophages resembling fibroblasts or myofibroblasts characterized by vimentin, CD45 (LCA), CD68 (KP1) or HAM-56, and HLA-DR(LN3) immunoreactivity and demonstrated production of procollagen-alpha1 (I) mRNA by in situ hybridization. Clonal T-cell receptor chain gene rearrangements were undetectable by polymerase chain reaction. Strong specific lymphocyte-derived interleukin-1beta and interleukin-6 mRNA cytokine transcripts were identified. Although all patients with IPT were managed with steroids and nonsteroidal anti-inflammatory medication, some had treatment-refractory disease. Because all-trans retinoic acid has been demonstrated to inhibit the in vitro transformation of monocytes into collagen-producing spindle-shaped macrophages ("neofibroblasts"), it may be of benefit for patients with IPT.
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PMID:Inflammatory pseudotumors of lymph node origin show macrophage- derived spindle cells and lymphocyte-derived cytokine transcripts without evidence of T-cell receptor gene rearrangements. Implications for pathogenesis and classification as an idiopathic retroperitoneal fibrosis-like sclerosing immune reaction. 860 85

The highly metastatic human melanoma cell line BLM was transfected with the E1A or E1A + E1B regions of adenovirus 5 (Ad5). A series of progression markers, correlated with the malignant phenotype of parental BLM (including calcyclin, thymosin beta 10, plasminogen activator inhibitors types 1 and 2, urokinase type and tissue type plasminogen activators, vimentin, tissue type transglutaminase, and interleukin-6), was collectively repressed in the transfectants, whereas several control genes were not affected or even induced. The apparently coordinate repression of a set of markers by the same regulator gene, Ad5 E1A in this case, suggests the existence of one pathway under the control of a main switch and predicts that one or more as yet unidentified cellular master genes normally exert this function. A reduced oncogenicity was observed after subcutaneous inoculation of the E1A transfectants into nude mice and provides additional evidence in support of a tumor suppressor function of Ad5 E1A.
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PMID:Simultaneous suppression of progression marker genes in the highly malignant human melanoma cell line BLM after transfection with the adenovirus-5 E1A gene. 878 Jun 94

Olfactory neuroepithelial cells (ONC) grown from biopsies of human donors are a novel cell culture system that may facilitate studies into normal and disease-related human neurobiology. We further characterized the expression of cell surface markers and intermediate filaments, and responses to neurotrophic factors by ONC. ONC are positive for cell surface markers N-CAM, PSA-N-CAM, neutral endopeptidase, N-aminopeptidase, NGF low-affinity receptor homologue (CD40), and transferrin receptor by flow cytometry for the intermediate filament proteins peripherin, vimentin, and NF-H by immunocytochemistry. Responses to neurotrophic factors measured were process outgrowth, cytoskeletal protein expression, and protein phosphorylation. Process outgrowth was increased by interleukin-beta 164-171 (IL-1beta) or by the combination of IL-1beta, interleukin-6 (IL-6), nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). This combination of IL-1beta, IL-6, NGF, and bFGF (16NF) increased expression of two cytoskeletal proteins, NF-H protein and microtubule-associated protein tau. Application of the individual neurotrophic factors IL-1beta, IL-6, NGF, and bFGF increased protein phosphorylation, while 16NF produced an immediate increase in tyrosine phosphorylation of several proteins (MW of 40-80, 120, 150, and 190 kDa). The 16NF combination appears to act through a tyrosine-kinase-mediated pathway to induce process extension and increase NF-H expression. The ONC culture has the potential to be further explored to examine the relationship among process outgrowth, protein phosphorylation, and synergy between neurotrophin and cytokine receptor systems.
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PMID:Human olfactory neuroepithelial cells: tyrosine phosphorylation and process extension are increased by the combination of IL-1beta, IL-6, NGF, and bFGF. 891 9

A novel epithelioid sarcoma (ES) cell line, designated as ES-OMC-MN, was established from a 44-year-old woman with recurrence and metastasis of ES. The cells were spindle-shaped or polygonal and were positive for cytokeratin and vimentin on immunohistochemical staining. Electron microscopy revealed desmosome-like structures between the cells. These characteristics were also noted in the original tumor. Southern blot analysis of HindIII digests showed an additional 8.0 kb band and an 8.8 kb band in DNA from the cultured cells and the original tumor as well as the peripheral blood cells of the patient, while only an 8.8 kb band was observed in control human placental DNA. There were no point mutations of N-ras codons 12, 13, and 61, suggesting that the abnormality of N-ras was not due to mutation but to polymorphism. Interleukin-6 (IL-6) was secreted into the culture medium at high levels. Recombinant IL-6 augmented the proliferation of these cells, while cell growth was inhibited by incubation with an anti-IL-6 antibody. The cells also expressed surface IL-6 receptors, indicating that IL-6 acted on this cell line in an autocrine manner. IL-6 and IL-6 receptors were also found in the original tumor. These results demonstrate that ES-OMC-MN cells retained all the morphological and biochemical characteristics of the original tumor and suggest that an autocrine effect of IL-6 may be involved in the development of ES.
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PMID:Establishment and characterization of an epithelioid sarcoma cell line with an autocrine response to interleukin-6. 914 39

The presence of GABA(A)-receptors on astrocytes was studied in explant and primary cultures of rat cerebellum, hippocampus and spinal cord by means of immunohistochemistry. For these studies we have used the monoclonal antibody bd 17 against the beta2- and beta3-subunits of GABA(A)-receptor. In explant cultures many neurones were intensely stained with the GABA(A)-receptor antibody whereas adjacent astrocytes revealed little or no immunoreactivity. In the far outgrowth zone of explant culture, however, many immunostained astrocytes were observed. In primary astrocyte cultures, only a few cells were stained by the antibody. Astrocytes which became reactive after producing an artificial scar or after addition of certain compounds such as dibutyryl cyclic AMP, interleukin-6, basic fibroblast growth factor and kainic acid, also revealed GABA(A)-receptor immunoreactivity. Furthermore, these astrocytes were intensely stained for glial fibrillary acidic protein and vimentin. From our studies we conclude that only a sub-population of normal astrocytes are immunopositive for the GABA(A)-receptor antibody whereas astrocytes which become reactive following injury of the tissue or after addition of dibutyryl cyclic AMP, the cytokine interleukin-6, fibroblast growth factor or the neurotoxin kainic acid express GABA(A)-sites.
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PMID:Expression of GABA(A) receptors by reactive astrocytes in explant and primary cultures of rat CNS. 964 26

An autopsy case of granulocyte colony-stimulating factor (G-CSF)- and interleukin-6 (IL-6)-producing diffuse deciduoid peritoneal mesothelioma is reported. The patient was a 70-year-old man with abdominal distension and weight loss in the year prior to his death. Laboratory data suggested severe inflammation with marked leukocytosis, thrombocytosis and elevated serum levels of C-reactive protein, G-CSF and IL-6. Imaging studies showed an expansive mass occupying the entire abdomen and pelvic cavity. Histological diagnosis of tissue taken by needle biopsy was difficult due to the unusual sarcomatoid-appearance of the tumor. In addition, there was severe infiltration of numerous neutrophilic leukocytes. An autopsy revealed that the diffuse peritoneal tumor had a fresh fishmeat-like appearance with focal mucinous degeneration and entirely encased the abdominal organs. Histological examination showed a sheet-like proliferation of tumor cells with large ovoid or polygonal cytoplasm, large atypical nuclei and obvious nucleoli. The tumor cells showed abundant glycogen and hyaluronic acid, and were immunoreactive to cytokeratin, calretinin, epithelial membrane antigen (EMA), CA-125, and focally to vimentin. The tumor cells were immunoreactive to G-CSF and IL-6. Electron microscopy revealed long, slender microvilli on the tumor cell surface. This tumor was diagnosed as a G-CSF- and IL-6-producing, diffuse deciduoid mesothelioma. We report this case with special reference to the differential diagnosis of deciduoid peritoneal mesothelioma with paraneoplastic syndrome.
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PMID:Granulocyte-colony stimulating factor- and interleukin 6-producing diffuse deciduoid peritoneal mesothelioma. 1530 18


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