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)

Human T cell leukemia virus type I-transformed T cell line HUT102 constitutively secreted soluble factors which induced differentiation of a murine myeloid leukemic cell line, M1, to increase the immune complex-binding and/or phagocytizing capacity. This macrophage differentiating factor(s) (MDF) was purified from the culture supernatants of HUT102 cells by using several steps of column chromatography and novel immune-adherence and/or immune-phagocytic assays. The finally purified MDF activity was detected in the fraction that consisted of 40,000- and 45,000- molecular weight molecules. Antibodies specific for human interleukin-6 or for human granulocyte-colony stimulating factor, both of which have differentiation-inducing activity on M1 cells when used as a single factor, could not neutralize the MDF activity. These findings suggest that the 40,000- and/or 45,000- molecular weight molecules in the HUT102 cell products may be possible novel differentiation-inducing factors acting on a murine macrophage lineage across the species barrier.
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PMID:A macrophage differentiating factor derived from human T cell line HUT102 acting on a mouse myeloid cell line M1. 812 28

Chronic ethanol ingestion predisposes to tuberculosis and bacterial pneumonia. Mycobacterium avium complex organisms cause bacteremia in patients with AIDS. Human macrophages and murine Kupffer cells exposed to ethanol are more permissive towards intracellular growth of M. avium than control mononuclear phagocytes. Ethanol also has been shown to impair the ability of human macrophages and murine Kupffer cells to respond to stimulation with tumor necrosis factor (TNF) and granulocyte macrophage colony stimulating factor (GM-CSF), and to produce cytokines such as interleukin-1, interleukin-6, and TNF when properly stimulated. The impairment is dependent in part on a downregulation in the number of TNF receptors on the macrophage's membrane. Recent evidence suggests that ethanol in nonlethal concentrations induces stress-related proteins in M. avium, leading to the inhibition of intracellular pathways in the macrophage and, consequently, impairing some of its functions. In summary, ethanol acts both on the host and on the mycobacterium in a complex sequence of events that influence the outcome of the infection.
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PMID:Effect of ethanol on the interaction between the macrophage and Mycobacterium avium. 820 5

Interleukin-6 (IL-6) is a pleiotropic cytokine that enhances the maturation of megakaryocytes. In mice, in vivo treatment with IL-6 results in elevated platelet counts both in untreated animals and after myelosuppressive therapy. In this study, we assessed the effect of continuous infusion of IL-6 in sublethally irradiated (7 Gy) mice on peripheral blood cell counts and progenitor cells in bone marrow and spleen. Female Swiss mice were treated by continuous infusion with 1 or 10 micrograms IL-6 per day for 7 or 14 days. Continuous infusion of IL-6 for 7 days resulted in elevated levels of circulating IL-6 (mean: 1872 pg/mL vs. 100 pg/mL for phosphate-buffered saline [PBS]-treated controls) and in an accelerated reconstitution of platelets starting at day 12 after irradiation. In IL-6-treated animals, the 50% pretreatment platelet count was reached on day 15 vs. day 21 for irradiated controls receiving no IL-6. Treatment with IL-6 for 14 days resulted in a further increase in platelet counts, exceeding the pretreatment counts. The number of colony-forming units-megakaryocyte (CFU-Mk) was significantly elevated from day 6 to 18 in the spleen but not in bone marrow. To assess the contribution of extramedullary megakaryocytopoiesis in the spleen to IL-6-induced platelet recovery, IL-6 was also administered to splenectomized mice. The stimulatory effect of IL-6 on platelet recovery was preserved in these animals, indicating that megakaryocytopoiesis in the spleen did not contribute to the accelerated recovery of platelets. The neutrophil counts were elevated during IL-6 treatment and became similar to controls after cessation of therapy, whereas the numbers of colony-forming units-granulocyte/macrophage (CFU-GM) in the bone marrow were elevated from day 9 to 24 in all animals treated with 10 micrograms IL-6 per day. In conclusion, continuous infusion of IL-6 stimulates platelet recovery after irradiation without increasing the number of CFU-Mk and conversely stimulates the proliferation of myeloid progenitor cells without an effect on neutrophil reconstitution.
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PMID:Continuous infusion of interleukin-6 in sublethally irradiated mice accelerates platelet reconstitution and the recovery of myeloid but not of megakaryocytic progenitor cells in bone marrow. 824 64

PTH and other hormones that stimulate resorption affect osteoclasts indirectly by modulating cytokine production by osteoblasts. However, the identity and role of the osteoblast-derived cytokines involved in this process are unclear. To examine which cytokines are regulated by PTH, we assessed cytokine mRNA levels in osteoblasts using the reverse transcription-polymerase chain reaction technique. Of the 16 cytokines we examined, unstimulated MC3T3-E1 osteoblastic cells expressed mRNA for interleukins 5, 6, and 7, macrophage and granulocyte-macrophage colony-stimulating factors, transforming growth factor beta 1, and leukemia inhibitory factor. PTH specifically increased expression of interleukin-6 (approximately 50-fold) and leukemia inhibitory factor (approximately 10-fold). Levels of both IL-6 and LIF mRNA peaked 30-60 minutes after addition of PTH and returned to baseline by 4-6 h. This rapid and transient mRNA response, which resembles that of immediate early genes, was also observed in primary rat osteoblasts. The transient mRNA response was accompanied by increased secretion of IL-6 protein. Lipopolysaccharide, another stimulator of resorption, increased mRNA levels of a group of cytokines that were not induced by PTH, namely interleukin-1 alpha, tumor necrosis factor alpha, and granulocyte-macrophage and granulocyte colony-stimulating factors. We conclude that osteoblasts produce complex networks of cytokines that (1) are regulated by bone-resorptive agents and (2) may be involved in controlling bone resorption.
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PMID:Regulation of cytokine expression in osteoblasts by parathyroid hormone: rapid stimulation of interleukin-6 and leukemia inhibitory factor mRNA. 825 53

It is often assumed that macrophage-colony stimulating factor (M-CSF) or CSF-1, as well as granulocyte macrophage-CSF (GM-CSF), can induce inflammatory mediator production by monocytes/macrophages. We demonstrate with elutriation-purified human monocytes that, in contrast to lipopolysaccharide, recombinant human CSF-1 does not induce secretion of prostaglandin E2, interleukin-6 (IL-6), IL-1 beta, or tumor necrosis factor alpha, as measured by immunoassay; however, increased urokinase-type plasminogen activator (u-PA) activity in cell lysates and mRNA was observed. Similar results were obtained when the monocytes were treated with recombinant human GM-CSF. Such increased u-PA expression may contribute to the function of CSF-1 at sites of inflammation.
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PMID:Effects of macrophage-colony stimulating factor on human monocytes: induction of expression of urokinase-type plasminogen activator, but not of secreted prostaglandin E2, interleukin-6, interleukin-1, or tumor necrosis factor-alpha. 831 54

Secretion of different cytokines may be an important T-cell effector mechanism for bone marrow engraftment, graft versus host disease and graft versus leukaemia effects after allogeneic bone marrow transplantation (BMT). Cytokine secretion and autocrine proliferative capacity of T-cell clones derived from leukaemia patients 3-6 weeks after allogeneic bone marrow transplantation were investigated. Only a minority of post-transplant T-cell clones (23/120; 19%) was capable of undergoing autocrine proliferation. By contrast, 21/65 (32%) normal control clones from the marrow donors derived under the same conditions were autocrine proliferative. All clones were interleukin-2 (IL-2) responsive. A majority (12/17; 71%) of autocrine proliferating post-transplant clones secreted detectable IL-2. Compared with control clones, CD4+ T-cell clones derived early after BMT produced decreased levels of interleukin-4 (IL-4) and interleukin-6 (IL-6), whereas secretion of interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) showed no significant difference. The small number (n = 8) of posttransplant CD8+ clones showed decreased production of IL-3, IL-4 and IL-6 compared with control clones, but normal secretion of GM-CSF. Neither CD4+ nor CD8+ T-cell clones secreted interleukin-7 (IL-7).
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PMID:Secretion of IL-2, IL-3, IL-4, IL-6 and GM-CSF by CD4+ and CD8+ TCR alpha beta+ T-cell clones derived early after allogeneic bone marrow transplantation. 832 61

After differentiation either with exogenous macrophage (M) or with granulocyte/macrophage (GM) colony-stimulating factor (CSF) microglial cells were isolated from neonatal mouse brain cell cultures and were comparatively tested for secretory immune effector cell functions. Both factors obviously do not promote the development of cells with biased growth requirement; however, the two microglia populations displayed distinct potentials to produce inflammatory cytokines. Upon gradual stimulation by lipopolysaccharide, the cells harvested from M-CSF-driven culture released more interleukin-1 and tumor necrosis factor activity, GM-CSF-grown cells on the contrary proved superior in interleukin-6 secretion. This pattern was paralleled by corresponding different kinetics of cytokine release in both types of microglial cells. When infected with Toxoplasma gondii only GM-CSF-differentiated cells were able to restrict the intracellular multiplication of tachyzoites in the absence of external stimuli. As described for interferon-gamma-treated macrophages, the antiparasitic activity of this microglia population is due to the synthesis of reactive nitrogen intermediates, since it was antagonized by NG-monomethyl-L-arginine, a competitive inhibitor of the arginine-dependent metabolic pathway. Complementary to previous data which attest an intrinsic capability for antigen presentation to GM-CSF-grown microglia, the functional state of the cells elicited by M-CSF and GM-CSF, respectively, may correspond to the resting and an activated form of microglia as distinguished in vivo.
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PMID:Functional dichotomy of mouse microglia developed in vitro: differential effects of macrophage and granulocyte/macrophage colony-stimulating factor on cytokine secretion and antitoxoplasmic activity. 833 Nov 61

Fibroblasts of the pulmonary interstitium are intimately involved in the response of the lung to inflammation as well as in repair of injured tissues. The response of fibroblasts within an inflammatory site appears to be directed, in part, by peptide mediators. Neutral endopeptidase (NEP), a metallopeptidase on the surface membrane of fibroblasts, can inactivate various vasoactive peptides, including kinins and tachykinins. Because lung fibroblasts both secrete cytokines and respond to mediators within the immediate environment, NEP might be regulated by locally generated cytokines. We found that several cytokines, including interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor, interleukin-6, and granulocyte macrophage colony-stimulating factor, enhanced activity of NEP on the surface of intact fibroblasts. In contrast, cultured pleural mesothelial cells had much lower levels of NEP than fibroblasts, and the enzyme was not enhanced by either IL-1 or TNF-alpha. Further studies with IL-1 showed that the effect required at least 6 h of exposure to the cytokine and depended upon final cytokine concentration. Combinations of IL-1 with other cytokines increased NEP activity beyond that in cells treated with individual cytokines, but combinations had less than additive effects. Selected pharmacologic agents indicated that the mechanism involves second messenger pathways. The cytokine effect on NEP was attenuated by indomethacin, an inhibitor of cyclooxygenase, by N-[2-(methylamino) ethyl]-5-isoquinolinesulfonamide dihydrochloride, an inhibitor of protein kinase, and by adenosine 3',5' cyclic monophosphothionate, an analog of cyclic adenosine monophosphate (cAMP) that competitively inhibits the cAMP signal pathway. It was mimicked by dibutyryl cAMP and by forskolin, an activator of adenyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokines increase neutral endopeptidase activity in lung fibroblasts. 838 Feb 49

In this study we evaluated the production of granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) by enriched bone marrow (BM) macrophages in 15 patients affected by myelodysplasia and 20 normal BM donors. The presence of GM-CSF, IL-6 and TNF-alpha in the culture supernatants of BM macrophages was detectable only after stimulation with lipopolysaccharide (LPS), whereas no differences were present in the amount of IL-6 and TNF-alpha between myelodysplastic patients and normal controls, GM-CSF production appeared eight-fold reduced in BM macrophage culture supernatants from myelodysplastic patients with respect to normal controls. After further experiments, we concluded that the impaired release of GM-CSF by BM macrophages could not be due to a different production kinetic in myelodysplastic patients. Moreover, the number of multipotent (CFU-GEMM), granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) progenitors was significantly impaired in myelodysplastic patients. In conclusion, we demonstrated that the production of GM-CSF by purified adherent cells from MDS patients is markedly impaired in spite of the peripheral blood cytopenia. This selective defect in GM-CSF production, along with an intrinsic defect of haematopoietic progenitor cells, might contribute to the impairment of haematopoiesis always observed in myelodysplastic patients.
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PMID:Impairment of GM-CSF production in myelodysplastic syndromes. 839 22

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


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