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)

Gamma interferon (IFN-gamma) is the product of multiple cell types within the bone marrow microenvironment and has been demonstrated to act as a potent inhibitor of myelopoiesis in vitro and in vivo. The action of this cytokine on lymphohematopoiesis has now been examined on both long-term bone marrow cultures and representative cloned cellular components of the bone marrow microenvironment. In myelopoietic (Dexter) cultures, the half maximal inhibitory concentration of IFN-gamma was between 1 and 10 U/mL. In comparable lymphopoietic (Whitlock/Witte) cultures, IFN-gamma inhibited the production of B-lineage lymphoid cells with a half maximal effective concentration of less than 1 U/mL. In a clonal assay for pre-B cells, IFN-gamma inhibited colony formation with a half maximal concentration of 1 to 5 U/mL. Not all B-lineage lymphoid cells displayed the same sensitivity, however. Growth of the IL-7-dependent B cell line (2E8) in methylcellulose assays was unaffected by IFN-gamma while the replication of other lymphoid lines was partially or completely inhibited. IFN-gamma induced the expression of cell surface proteins (MHC Class I and II) on both B-lineage cells and stromal cells. In cloned stromal cell lines, IFN-gamma increased the steady state mRNA levels for the cytokines interleukin-6 (IL-6) and JE, a member of the IL-8 family. These data indicate that IFN-gamma acts within the lymphohematopoietic microenvironment through both direct and indirect actions on the hemopoietic and stromal cell populations.
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PMID:Modulation of lymphohematopoiesis in long-term cultures by gamma interferon: direct and indirect action on lymphoid and stromal cells. 842 61

Colostrum and blood samples were obtained on postpartum day 2 and 3 from 17 lactating, healthy women. After delipidation and molecular sieving fractionation of colostrum, interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) could be readily measured by using a sensitive immunoassay. Antiviral activity could be also measured in some colostrum samples suggesting that interferon was biologically active. On the contrary, corresponding plasma samples showed negligible activity. These results expand previous data showing the presence of IL-1, tumor necrosis factor (TNF-alpha), and IL-6 in normal colostrum and are in line with the concept of a basal cytokine production in physiological conditions. All of these cytokines probably act on the oropharyngeal and gut-associated lymphoid tissue of the newborn and favor the development and maturation of the immune system.
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PMID:Presence of interferon-gamma and interleukin-6 in colostrum of normal women. 845 28

Prostate tumor cells preferentially metastasize to bony sites and lymph nodes at a frequency in excess of that which would be predicted by random tumor cell dissemination. In order to determine whether chemoattractants in these organs promote organ-specific metastasis, we utilized human cell lines derived from and/or related to these organs as sources of potential chemoattractants. Secretory proteins derived from the cell lines MG-63 (osteosarcoma), SK-ES-1 (Ewing's sarcoma), and KG-1 (leukemia) stimulated chemomigration of the TSU-pr1 prostate tumor cells in a dose-dependent manner in Boyden chambers. In addition, secretory proteins from a human prostatic stromal cell line (hPS) and from the TSU-Pr1 prostate tumor cell line were also able to stimulate chemomigration of the TSU-pr1 cells through Boyden chambers. Since lymph nodes and bony sites represent organs of hematopoietic/lymphoid proliferation and activation, we undertook identification of specific cytokines present at these sites which may promote the chemomigration of prostate tumor cells. In this context, the cytokines interleukin-1 alpha, interleukin-2, interleukin-6, tumor necrosis factor-beta, transforming growth factor-beta, interferon alpha 2-a, and granulocyte-macrophage colony-stimulating factor did not stimulate chemomigration of the TSU-pr1 prostate tumor cell line. In contrast, the cytokine epidermal growth factor (EGF) stimulated chemomigration of the TSU-pr1 prostate tumor cells through the Boyden chambers in a dose-dependent manner. Western blot analysis of secretory proteins from the cell lines KG-1, SK-ES-1, MG-63, hPS, and TSU-pr1 identified EGF-immunoreactive proteins in all cases. In addition, EGF immunoreactivity was localized to the stroma of the human prostate, the osteogenic stroma of pelvic medullary bone, and the stroma within the capsule and trabeculae of pelvic lymph nodes. Hence, these results demonstrate that the cytokine EGF promotes the chemomigration of the TSU-pr1 prostate tumor cell line, and that EGF within the stroma of pelvic lymph nodes and medullary bone may act as a chemoattractant for prostate tumor cells, thereby facilitating the preferential formation of metastatic foci within these organs.
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PMID:Epidermal growth factor (EGF) promotes chemomigration of a human prostate tumor cell line, and EGF immunoreactive proteins are present at sites of metastasis in the stroma of lymph nodes and medullary bone. 854 75

We have previously found that dimethyl sulfoxide (DMSO), a known inducer of differentiation in several kinds of myeloid cells, arrests proliferation of human lymphoid cells including Raji and Akata Burkitt's lymphoma cells at the G1 phase. We investigated whether DMSO affects cell proliferation and differentiation of the lymphoid cell line SKW6-CL4, which is capable of differentiating terminally into IgM-producing cells. As in the case of Raji, Akata, and Molt-4, the proliferation of SKW6-CL4 was reversibly arrested at the G1 phase by treatment with 2% DMSO for 5 days even in the presence of interleukin-6 (IL-6). DMSO inhibited spontaneous IgM secretion as well as IL-6-induced IgM production in SKW6-CL4 at a concentration lower than that affecting cell proliferation. Of the cell-surface differentiation markers CD10, CD20, CD21, and CD23, the expression of CD20 was suppressed by DMSO treatment, and partial restoration of the expression was observed 24 to 48 h after release from DMSO. The level of IL-6 receptor protein was not affected by DMSO treatment. These results indicate that DMSO not only arrests the cell cycle of a human lymphoid cell line SKW6-CL4 at the G1 phase but also inhibits the differentiation into IgM-secreting cells at a concentration lower than that affecting cell proliferation and that DMSO overcomes the effect of IL-6 on terminal differentiation of SKW6-CL4. As a whole, proliferation of human lymphoblastoid cell lines was revealed to be reversibly arrested at the G1 phase by DMSO, which is known to induce differentiation in several myeloid cells, without inducing cell differentiation.
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PMID:Reversible G1 arrest induced by dimethyl sulfoxide in human lymphoid cell lines: dimethyl sulfoxide inhibits IL-6-induced differentiation of SKW6-CL4 into IgM-secreting plasma cells. 854 66

Skin sensitization with chemical allergens is associated with the activation and proliferation of T lymphocytes within lymph nodes draining the site of exposure. These events are accompanied by the secretion of interleukin-6 (IL-6) by lymph node cells (LNC). We have investigated the cellular source of IL-6 seventy-two hours following primary exposure of mice to the contact allergen oxazolone. Immunocytochemical analyses of sections of activated lymph nodes have revealed that cells expressing IL-6 are located within the T-dependent lymph node paracortex, with none present in lymphoid follicles. Cells which expressed IL-6 cofractionated exclusively with LNC of low buoyant density, the majority of which also expressed membrane Ia and had a dendritic morphology. Depletion of dendritic cells from LNC culture was associated with a significant decrease in the secretion of IL-6 by the residual population. These data demonstrate that dendritic cells are a major source of IL-6 within lymph nodes during primary immune responses to cutaneous antigens.
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PMID:Identification of dendritic cells as a major source of interleukin-6 in draining lymph nodes following skin sensitization of mice. 855 83

The cytokine interleukin-6 (IL-6) is a multi-functional small peptide molecule that is produced by various types of lymphoid and non-lymphoid cells and plays a central role in hematopoiesis, host defense mechanisms, and acute phase reactions, including regulation of inflammatory and immune responses. A high-sensitivity ELISA assay was applied to serum (S) and urine (U) samples available from 10 men (median age = 50y, range = 46-71y) in order to compare circadian characteristics of IL-6 between assays and in 2 biological fluids. S and U samples were collected at 3-h intervals for 24hrs beginning at 19:00h on May 14, 1993 (8 samples/subj) and frozen at -25 degrees C until analysis. IL-6 in U was adjusted for time & volume (pg/hr) and assigned to midpoint of collection interval. A significant time-effect was found by ANOVA and a high-amplitude circadian rhythm was detected by the least-squares fit of a 24-hr &/or 24+12-hr cosine for each assay. Higher serum IL-6 values were detected throughout the night, with a peak at 01:00h, and lower values throughout the day, with a nadir at 10:00h. In contrast, IL-6 values in urine were highest during the day, with a major peak in the afternoon at 17:30h and a minor peak at 08:30h, and lowest values overnight, with a nadir at 23:30h. Of interest, the rhythm in urinary IL-6 concentration (pg/ml) was more prominent than hourly excretion rate (pg/hr). Thus, endogenous IL-6 (and possibly other cytokine) levels may be significantly influenced by their large and predictable day-night variations and the biological fluid used.
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PMID:Circadian characteristics of interleukin-6 in blood and urine of clinically healthy men. 855 32

Oncostatin M (OSM) is a member of the interleukin-6 (IL6)-related cytokine subfamily that includes IL6, IL11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor and cardiotrophin-1. While human OSM has been characterized and the bovine OSM gene was recently cloned, the murine counterpart had not been identified. Here we describe molecular cloning of murine OSM as an immediate early gene induced by a subset of cytokines including IL2, IL3 and erythropoietin (EPO) in myeloid and lymphoid cell lines. The induction kinetics of OSM are rapid and transient, reaching a maximal level within 30-60 min and decreasing thereafter. Induction of OSM depends on the signals generated by the membrane-proximal region of the EPO receptor as well as that of the beta chain of the IL3/GM-CSF receptor, which activate JAK2 and STAT5. About 100 bases upstream of the transcription initiation site of the OSM gene contains a possible STAT5 binding site which is essential for IL2, IL3 and EPO-dependent promoter activity of the OSM gene. Expression of STAT5 and the EPO receptor in COS cells conferred EPO-dependent activation of the OSM promoter. Moreover, the mutant IL2 receptor lacking the ability to activate STAT5 induced c-myc but failed to induce OSM. Thus OSM is one of the common targets of a subset of cytokines that activate STAT5. The murine OSM gene is located near to the LIF gene, expressed at high levels in bone marrow and possesses similar biological activity to human OSM. Identification of murine OSM as a cytokine-inducible immediate early gene provides a new insight into the physiological function of this unique cytokine.
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PMID:Mouse oncostatin M: an immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway. 860 75

We investigated the expression of interleukin-6 (IL-6) mRNA in tumours from 21 patients with B-cell non-Hodgkin's lymphoma (NHL). Total RNA, extracted from diagnostic tissue specimens, was subjected to semi-quantitative analysis for IL-6 mRNA by the reverse transcription-polymerase chain reaction (RT-PCR). The amount of IL-6 mRNA ws semi-quantified against that in pokeweed mitogen (PWM) stimulated peripheral blood mononuclear cells. The expression of IL-6 in neoplastic B cells was confirmed by immunohistochemistry. We then looked for correlations between the amount of IL-6 concentrations. The amount of IL-6 mRNA correlated with the circulating IL-6 concentration, suggesting that the malignant cells were the source of IL-6 in these patients with B-cell NHL. Our results suggest that the circulating IL-6 in patients with B-cell NHL is derived from the neoplastic lymphoid cells, and that neoplastic cells may act as modulators of the general status of patients with B-cell NHL.
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PMID:Elevated serum interleukin-6 (IL-6) is derived from neoplastic lymphoid cells in patients with B-cell non-Hodgkin's lymphoma: correlation with extent of IL-6 expression and serum concentration. 861 61

To determine the frequencies and differential counts of megakaryocytes after cytoreductive treatment in nucleated low-density (1.060 g/ml) bone marrow cells (BMNC) of dogs an immunogold-silver staining (IGSS) technique with the lineage specific monoclonal antibody 2F9 was established. This antibody recognizes the glycoprotein IIb/IIIa complex expressed on the surface of canine megakaryocytes and platelets. The IGSS technique enables not only the detection of megakaryocytes occurring at a low frequency (0.1-0.2%), but also the discrimination between the different maturation stages of megakaryocytes due to cell size, nuclear morphology and cytoplasmic staining. By the use of this technique, small lymphoid megakaryocytic cells were identified. Comparable numbers of megakaryocyte colony-forming cells in 2F9-depleted and nondepleted BMNC suspensions (25.7 +/- 5.0 vs. 25.3 +/- 5.1 Meg-CFC/10(5) BMNC) indicate that these small 2F9 positive cells are nonclonogenic precursors of megakaryoblasts. To prove the applicability of IGSS, serial examinations of bone marrow samples from dogs treated with recombinant human interleukin-6 (IL-6) after exposure to 2.4 Gy total body irradiation (TBI) were performed. The results of the microscopic evaluation indicate that, in the recovery phase after TBI, IL-6 induced an earlier and stronger increase in megakaryocyte frequency in comparison to the control. Interestingly, all maturation stages of the megakaryocytic lineage took part in this IL-6 induced improvement of megakaryocyte recovery.
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PMID:Investigation of megakaryopoiesis in myelosuppressed bone marrow using immunogold-silver staining (IGSS). 864 3

Although the expression and function of CD40 on B lymphocytes has been well studied, the significance of CD40 on non-lymphoid cells such as keratinocytes (KC) is not as well characterized. We demonstrate in this report that CD40 is expressed by virtually all human KC, and that it functions as an important signaling molecule. Flow cytometry of undifferentiated and terminally differentiated KC indicated that both cell types expressed CD40, as determined by binding to monoclonal antibodies and a recombinant CD40 ligand fusion protein; interferon-gamma (IFN-gamma) treatment of KC increased CD40 expression. Cultured KC also expressed 1.5-kb CD40 transcripts. Activation of KC cell surface CD40 using the monoclonal antibody G28.5 resulted in the rapid generation of a 50-kDa tyrosine phosphorylated polypeptide, as well as a dose-dependent increase in the secretion of interleukin-6, a cytokine that has been linked to KC proliferation. KC also co-stimulated a significant T lymphocyte proliferative response to the mitogen phytohemagglutinin that was CD40 dependent. These data indicate that KC constitutively express a low level of functional CD40 and regulate their expression in response to IFN-gamma. These data support the concept that KC, via their expression of CD40, have the capacity to amplify inflammation in the skin by interacting with CD40 ligand-bearing T cells.
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PMID:Human epidermal keratinocytes are induced to secrete interleukin-6 and co-stimulate T lymphocyte proliferation by a CD40-dependent mechanism. 864 19


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