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)

The trophoblast, an epithelial cell of fetal origin that forms the physical barrier between the mother and developing conceptus, becomes a component of the host immune system during pregnancy. Of the classical immune cells, it most closely resembles the macrophage, also present in high numbers in the pregnant uterus. The macrophage and trophoblast, as cell classes, share characteristics such as phagocytosis, syncytialization, invasiveness, expression of the proteins CD4, CD14, IgG receptor (FcR), non-specific esterase, granulocyte macrophage-CSF (GM-CSF), colony stimulating factor 1 (CSF-1), interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF-alpha), transforming growth factors (TGF), platelet-alpha derived growth factor (PDGF) and receptors for these cytokines. In the uterus both cell types appear regulated by a common element, the uterine epithelium, that secretes cytokines such as CSF-1, GM-CSF, TNF alpha, TGF beta, IL-6, and leukaemia inhibitory factor (LIF) that target both macrophages and trophoblasts. The common characteristics and regulation that make teleological sense in terms of co-ordinating local uterine immunity during pregnancy may also be important in transmission of congenital diseases such as AIDS. The production by the uterine epithelium of a number of cytokines previously only associated with mononuclear phagocyte production and function predicts the existence of a similar, but broader, shared cytokine network encompassing trophoblast and the principal immune regulatory cell, the T lymphocyte.
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PMID:The trophoblast as an integral component of a macrophage-cytokine network. 843 11

Azidothymidine (AZT) has been demonstrated to increase platelet counts in patients suffering from acquired immunodeficiency syndrome (AIDS). However, the ability of long-term AZT treatment to sustain increases in platelet counts is controversial. We have recently demonstrated that AZT elevates the levels of circulating platelets in both normal C57BL/6 mice and mice made immunodeficient by infection with LP-BM5 murine leukemia virus (MAIDS mice). We therefore studied the effect of long-term AZT administration on platelet formation in both normal and MAIDS mice. Peripheral blood indices, levels of femoral and splenic megakaryocyte colony forming units (CFU-MK), and plasma levels of cytokines important in platelet formation-interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF)--were examined. Platelet counts remained elevated throughout a 120-day AZT treatment period. Splenic CFU-MK were not significantly changed in MAIDS mice, except at day 15 when they were elevated. Splenic CFU-MK were significantly decreased in normal mice at days 8 and 120, and increased at day 30. Bone marrow CFU-MK were increased by AZT treatment at all time points tested in both normal and MAIDS mice. Plasma levels of GM-CSF were unchanged by AZT treatment in both normal and MAIDS mice. Plasma levels of IL-6 were unchanged in AZT-treated normal mice but decreased in AZT-treated MAIDS mice. These results indicate that long-term AZT treatment maintains elevated levels of platelets in both normal and MAIDS mice and affects CFU-MK colony formation. Our studies add to a growing body of work suggesting that AZT can ameliorate thrombocytopenia associated with HIV disease.
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PMID:Sustained elevation of platelet counts by long-term azidothymidine treatment of immunosuppressed mice. 845 34

Cachexia is a common problem in the clinical management of cancer patients, particularly those with solid tumors. Cachexia is most obviously manifested as weight loss with massive depletion of both adipose tissue and muscle mass, and death is probably due to loss of lean body tissue. Not only is the survival time shorter in patients with cachexia, but the frequency of response to chemotherapy is also significantly reduced. Although anorexia frequently accompanies cachexia, attempts to halt or reverse cachexia by nutritional repletion have not been successful. This suggests that cachexia is due to metabolic abnormalities produced by the tumor in addition to the underlying anorexia. In some patients weight loss is associated with an increased relative energy expenditure possibly through an elevated adrenergic state. Several factors have been postulated as mediators of cancer cachexia and can be divided into two groups. (i) Materials with hormone-like characteristics which result in direct catabolism of host tissues. (ii) Cytokines which cause alterations in host metabolism indirectly. Included in group (i) are the conventional catabolic hormones and a lipid mobilizing factor (LMF) produced by tumors, which causes direct breakdown of adipose tissue. Included in group (ii) are tumor necrosis factor-alpha, interleukin-6, interferon-gamma and leukaemia inhibitory factor. The materials appear to influence adipose tissue indirectly through an inhibition of lipoprotein lipase. Reversal of cachexia has been achieved by two groups of agents. (i) Those stimulating food intake, e.g. megestrol acetate. (ii) Those directly inhibiting the LMF, e.g. eicosapentaenoic acid. While agents in group (i) can cause tumor growth stimulation, those in group (ii) act as tumor growth inhibitors. This latter results suggests that the products of catabolism of host tissues may be important for tumor growth and provides a new avenue for chemotherapeutic intervention.
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PMID:Cancer cachexia. 849 Jan 91

The acute phase response is defined as a large number of diverse reactions which attempt to adjust the organism to the effects of stress/injury. It is now clear that there is a complex interaction between the cytokines with interleukin-6 predominant, but also involving interleukin-1, tumor necrosis factor and a group of recently described cytokines including as well interleukin-11, leukaemia inhibitory factor and oncostatin M all of which influence the levels of acute phase proteins. In clinical practice, C reactive protein (CRP) is frequently used as marker of the acute-phase response. It has a short half-life and consequently it is a sensitive measure of cytokine-induced protein synthesis. In rheumatoid arthritis (RA) the rate appearance of bony erosions in the early phase of the disease correlated with the mean serum concentration of CRP in some studies. A recent study examining the rate of spinal trabecular bone loss in the first year of rheumatoid disease found a strong correlation between bone loss and serum CRP concentrations. It appears that CRP concentrations reflect the level of "systemic osteoclast-activating factor" and are, therefore, a good measure of the general catabolic state of the patient. Many would now consider that persistently elevated serum CRP in patients with RA is in itself an indication for immunosuppressive therapy.
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PMID:[Usefulness of the determination of C reactive protein and other acute phase proteins in rheumatoid arthritis]. 853 81

Embryonic hematopoiesis is initiated in part in the blood islands of the yolk sac. Previous confocal microscopic analysis has shown that the CD34 antigen, a mucin-like cell surface glycoprotein that is expressed by hematopoietic progenitors and all endothelial cells of the adult and embryo, is also found on a subset of luminal hematopoietic-like cells in the yolk sac blood islands as well as on the vascular endothelium lining these early hematopoietic locations. We show here that, as in all other hematopoietic sites thus far examined, immunoaffinity-purified CD34+ nonadherent cells from murine yolk sacs contain the vast majority of erythroid and myeloid progenitor cell colony forming activity. To examine the developmental interactions between these CD34+ hematopoietic progenitor cells of the yolk sac and the CD34+ yolk sac endothelium, we have immunaffinity-purified adherent endothelial cells from day 10.5 yolk sacs using CD34 antiserum and produced cell lines by transformation with a retrovirus expressing the polyoma middle T antigen. Analysis of these cell lines for CD34, von Willebrand's factor, FLK 1 and FLT 1 expression, and capillary growth in Matrigel indicates that they appear to be endothelial cells, consistent with their original phenotype in vivo. Coculture of yolk sac CD34+ hematopoietic cells on these endothelial cell lines results in up to a 60-fold increase in total hematopoietic cell number after approximately 8 days. Analysis of these expanded hematopoietic cells showed that the majority were of the monocyte/macrophage lineage. In addition, examination of the cultures showed the rapid formation of numerous cobblestone areas, a previously described morphologic entity thought to be representative of early pluripotential stem cells. Scrutiny of the ability of these endothelial cell lines to expand committed progenitor cells showed up to a sixfold increase in erythroid and myeloid colony-forming cells after 3 to 6 days in culture, consistent with the notion that these embryonic endothelial cells mediate the expansion of these precursor cells. Polymerase chain reaction analyses showed that most of the cell lines produce FLK-2/FLT-3 ligand, stem cell factor, macrophage colony-stimulating factor, leukemia-inhibitory factor, and interleukin-6 (IL-6), whereas there is a generally low or not measurable production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IL-1, IL-3, transforming growth factor beta-1, erythropoietin, or thrombopoietin. The output of mature hematopoietic cells from these cocultures can be modified to include an erythroid population by the addition of exogenous erythropoietin. These data suggest that endothelial cell lines derived form the yolk sac provide an appropriate hematopoietic environment for the expansion and differentiation of yolk sac progenitor cells into at least the myeloid and erythroid lineages.
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PMID:CD34+ endothelial cell lines derived from murine yolk sac induce the proliferation and differentiation of yolk sac CD34+ hematopoietic progenitors. 854 34

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

Potential mediators of hepatic metallothionein (MT) synthesis in adjuvant-induced arthritis were investigated in cultured rat hepatocytes. Sera from arthritic rats (14 d post-adjuvant treatment) in the presence of Zn (50 mumol/L)+dexamethasone (Dex; 1 mumol/L) increased metallothionein (MT) accumulation by 34% above that obtained with control rat serum with Zn+Dex. Endogenous IL-6 activity in serum from arthritic rats was 93 +/- 49 U/mL and was undetectable in control rat serum. The activities of TNF, IL-1 and corticosterone concentrations were the same in control and arthritic rats. The accumulation of MT in hepatocytes in the presence of Zn (10 mumol/L)+Dex (1 mumol/L) was enhanced 29% and 49% by media from lipopolysaccharide (LPS)-stimulated peritoneal macrophage (PMM) and Kupffer cell cultures (KCM), respectively. The response with PMM and KCM was quantitatively the same as that with interleukin-6 (IL-6). Analysis of PMM and KCM showed activities of 1,000-10,000 U/mL for IL-6, 100-1000 U/mL for TNF and < 10,000 U/mL for IL-1, the latter detected only in PMM. LPS alone enhanced the accumulation of MT above Zn+Dex in a dose dependent manner. A significant LPS response was obtained at 5 mg/L with a maximal stimulation above Zn+Dex of 38% at 10 mg/L. This direct stimulation of MT by LPS was not part of the response observed with PMM and KCM where the final LPS concentration in culture was only 0.1 mg/L. Other cytokines capable of synergy with Zn+Dex on MT synthesis were investigated. Interleukin-11 (IL-11) increased the Zn+Dex induction in a dose dependent manner with maximal stimulation at 100 U/mL of 40%. A small stimulation of 12% above Zn+Dex was obtained with leukaemia inhibitory factor (LIF) at concentrations greater than 100 U/mL. No enhancement of the Zn+Dex response was obtained with interleukin-3 (1000 U/mL), interleukin-4 (10 micrograms/L), platelet activating factor (5 nmol/L) or granulocyte-colony stimulating factor (5 micrograms/L). Neither IL-11 nor LIF enhanced the response obtained with Zn+Dex+IL-6. The results demonstrate that mediators present in arthritic rat serum and in LPS-stimulated PMM and KCM cause a quantitatively similar response on MT accumulation as IL-6. IL-11 and to a lesser extent LIF, are also potential mediators of MT synthesis in inflammation.
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PMID:Metallothionein induction in cultured rat hepatocytes by arthritic rat serum, activated macrophages, interleukin-6, interleukin-11 and leukaemia inhibitory factor. 859 81

Cancer cachexia is a syndrome of progressive wasting which has been suggested to be mediated by tumour-necrosis factor-alpha, interleukins 1 and 6, interferon-gamma and leukaemia-inhibitory factor. It has proved difficult to correlate levels of tumour-necrosis factor-alpha and interleukin-6 with cancer cachexia, and the weight loss induced by leukaemia-inhibitory factor may be due to toxicity. In the murine adenocarcinoma MAC16, cachexia is mediated by circulatory catabolic factors, which we have now isolated using an antibody cloned from splenocytes of mice transplanted with the MAC16 tumour, with a delayed cachexia. The material is a proteoglycan of relative molecular mass 24K which produces cachexia in vivo by inducing catabolism of skeletal muscle. The 24K material was also present in urine of cachectic cancer patients, but was absent from normal subjects, patients with weight loss due to trauma, and cancer patients with little or no weight loss. This suggests that cachexia in mice and humans may be produced by the same material.
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PMID:Characterization of a cancer cachectic factor. 860 22

In this study the distribution and quantitation of the flt3/flk-2 receptor was examined on bone marrow cells and defined haemopoietic subpopulations. Undifferentiated cells expressed the greatest numbers of flt3/flk-2 receptors: 19% of primitive lin-kit+sca-1+ bone marrow cells and 16% of fetal liver lin-aa4.1+ cells exhibited over 15 000 receptors per cell as determined by binding of the radiolabeled cognate ligand (flt3/flk-2 ligand, FL). Moderate binding was demonstrated on early B lymphocyte subsets (4400 receptors per cell) and very low levels were detected on monocytes. Binding was not detected on promyelocytes, myelocytes, promonocytes, metamyelocytes, polymorphonuclear cells, eosinophils or nucleated erythroid cells. FL enhanced the survival of primitive lin kit+sca-1+ cells with an efficacy s with an efficacy equivalent to stem cell factor (SCF). FL stimulated predominantly blast and granulocyte-macrophage colony formation in cultures of bone marrow cells by both direct and indirect mechanisms. Marked synergistic effects of FL with combinations of colony stimulating factors (CSFs) or interleukin-6 occurred in the proliferation of primitive lin-kit+sca-1+ cells, but not lin-kit+sca-1- progenitor cells. Surprisingly, recloning experiments revealed that FL plus IL-3 increased the generation of progenitor cells by lin-kit a-1- cells compared with SCF plus IL-3. Thus FL functions as a factor with both direct and indirect stimulatory activities directed to the expansion, maintenance of clonogenic potential, and possibly limited self-renewal, of early haemopoietic cells.
Leukemia 1995 Dec
PMID:The flt3/flk-2 ligand: receptor distribution and action on murine haemopoietic cell survival and proliferation. 860 17

Osteoblasts and their precursors respond to specific cytokines, growth factors, and hormones. One facet of this response includes the secretion of additional cytokines, some of which are part of the circuitry involved in the regulation of osteoblast and osteoclast function. Therefore, understanding which cytokines are able to activate osteoblastic cells and the consequences of that activation are central to understanding normal and pathologic bone remodeling. Oncostatin M (OSM) is a glycoprotein belonging to a new subfamily of cytokines related by sequence and structural homology and the use of the signal transducing receptor component gp130. Osteoblastic cells secrete and respond to leukemia-inhibiting factor (LIF) both in vitro and in vivo, suggesting that LIF is an autocrine regulatory factor. OSM is closely related to LIF, and therefore we hypothesized that OSM should regulate the function of cells in the osteoblastic lineage. Primary neonatal murine or fetal rat calvarial osteoblastic cultures were treated with OSM or LIF and a series of biochemical and biological parameters were determined. In these cultures, OSM induced proliferation, collagen synthesis, and interleukin-6 secretion, whereas it inhibited alkaline phosphatase activity. Bone resorption was also inhibited by OSM. These data represent the first report of OSM's effects on bone cell function and indicate that, like some other members of the LIF/interleukin-6 subfamily, OSM has potent bone regulatory activity.
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PMID:Oncostatin-M: a new bone active cytokine that activates osteoblasts and inhibits bone resorption. 862 82


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